Dissertations / Theses: 'HLA class II geners'

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Sukiennicki, Teresa Lyn. "Regulation of expression of the HLA class II gene, DQB1 /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/8358.

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Wu, Zhonglin. "Molecular analysis of HLA class II genes : from Hashimoto's thyroiditis to thyrocytes." Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265188.

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Jonson, Carl-Oscar. "The Importance of CTLA-4 and HLA Class II for Type 1 Diabetes Immunology." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1020s.pdf.

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Gil, Julio Miranda. "Estudo da associação entre os alelos DR e DQ de antígenos de histocompatibilidade leucocitária (HLA) e pênfigo vulgar em pacientes brasileiros." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-10012017-105831/.

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INTRODUÇÃO: Pênfigo Vulgar é uma doença bolhosa mucocutânea autoimune caracterizada pela formação de bolhas ou ulcerações dolorosas que afetam as superfícies cutâneas e/ou mucosas. A perda do contato célulacélula entre os queratinócitos do epitélio (acantólise) resulta na manifestação clínica do Pênfigo Vulgar. Autoanticorpos IgG se ligam às desmogleínas - anti-desmogleína 3 (Dsg3) e/ou anti-desmogleína 1 (Dsg1) -e são críticos na patogênese da doença. A predisposição genética ao PV, principalmente com alelos HLA DR e DQ, foi revelada desde a década de 80 e foi comprovada por análises genéticas e sorológicas, repetidas vezes. As características singulares da população brasileira favorecem estudos genéticos exploratórios. PACIENTES E MÉTODO: O grupo em estudo incluiu 51 pacientes com diagnóstico confirmado de Pênfigo Vulgar de um hospital terciário da cidade de São Paulo, estado de São Paulo, sudeste do Brasil. Foi realizada a extração de DNA e a tipificação de HLA A, B, C, DR e DQ por meio de kits QIagen (QIAamp DNA Mini Kit®). O grupo controle foi composto a partir de um banco de dados de 297 doadores falecidos não relacionados da cidade de São Paulo, que foram tipados pelo mesmo método. Este banco faz parte do Sistema Estadual de Transplantes da Secretaria de Saúde do Governo do Estado de São Paulo e contém a idade do paciente na coleta. O nível de significância dos testes estatísticos foi ajustado pela correção de Bonferroni, dependendo da quantidade de frequências fenotípicas avaliadas para o HLA A, HLA B, HLA C, HLA DRB1 e HLA DQB1. RESULTADOS: Os alelos HLAB* 57, HLA-C*15, HLA-DRB1*04:02, HLA-DRB1*08:04, HLA-DRB1*14:01, DQA1*03:01, DQB1*03:02 e o DQB1*05:03 estiveram associados com a susceptibilidade. Ambos os alelos HLA DRB1*04:02 e HLA-DRB1*14:01 e seus respectivos haplótipos DRB1*04-DQA1*03:01-DQB1*03:02 e DRB1*14- DQA1*01:01-DQB1*05:03 conferiram risco à doença. DISCUSSÃO: Os alelos DRB1*04:02 e DQB1*05:03 estão associados com o Pênfigo Vulgar no presente estudo, bem como a diversas populações do mundo. A associação aqui estudada com o DRB1*08:04 foi confirmada por causa deste alelo específico e não do desequilíbrio de ligação a algum gene adjacente. A associação do alelo HLA-B*57 ao pênfigo vulgar é reportada pela primeira vez pelo presente estudo. CONCLUSÕES: Os alelos HLA-B*57, HLA-C*15, HLADRB1* 04:02, HLA-DRB1*08:04, HLA-DRB1*14:01, DQA1*03:01, DQB1*03:02 e DQB1*05:03 estão associados ao Pênfigo Vulgar em pacientes brasileiros
BACKGROUND: Pemphigus vulgaris is a mucocutaneous blistering autoimune disease that manifests as painful blisters or ulcerations on the skin and/or mucosal surfaces. The loss of cell-cell adhesion among the epithelial keratinocytes (acantholisis) leads to pemphigus vulgaris clinical findings. IgG autoantibodies target desmoglein - anti-Desmoglein 3 (Dsg3) and/or 1 (Dsg1) - play a major role in the disease pathogenesis. Genetic predisposal to pemphigus vulgaris, especially the HLA DR and DQ alleles, was revealed since the 80s and has been proven through genetic and serologic analysis repeatedly. The unique constitution of the Brazilian population favours genetics exploratory studies. PATIENTS AND METHODS: The study group included fifty-one patients with confirmed diagnosis of Pemphigus Vulgaris from a tertiary hospital in Sao Paulo\'s city and state, southeast Brazil. DNA extraction and HLA A, B, C, DR and DQ typing using Qiagen kits (QIAamp DNA Mini Kit®). The control group was composed by a database of 297 unrelated deceased donors from the city of São Paulo that were typed through the same method. This database is a part of the Transplants State System of the Government\'s Health Secretary from the State of Sao Paulo. The statistical significance level was adjusted by using the Bonferroni correction depending on the phenotypic frequencies evaluated to HLA A, HLA B, HLA C, HLA DRB1 e HLA DQB1. RESULTS: The alleles HLA-B*57, HLA-C*15, HLADRB1* 04:02, HLA-DRB1*08:04, HLA-DRB1*14:01, DQA1*03:01, DQB1*03:02 and DQB1*05:03 were associated with susceptibility. Both alleles HLA DRB1*04:02 and HLA-DRB1*14:01 and their respective haplotypes DRB1*04-DQA1*03:01-DQB1*03:02 and DRB1*14-DQA1*01:01-DQB1*05:03 conferred risk to the disease. DISCUSSION: The DRB1*04:02 and DQB1*05:03 alleles are associated with Pemphigus Vulgaris in our study, as well in various populations. The association in our study with HLA-DRB1*08:04 was confirmed to be specific to this allele and not to linkage disequilibrium to any adjacent gene. The association between HLA-B*57 and pemphigus vulgaris is being reported for the first time at the present study. CONCLUSIONS: The alleles HLA-B*57, HLA-C*15, HLA-DRB1*04:02, HLADRB1* 08:04, HLA-DRB1*14:01, DQA1*03:01, DQB1*03:02 and DQB1*05:03 were associated with Pemphigus Vulgaris in Brazilian patients

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Weber, Raimar. "Estudo da associação entre antígenos de histocompatibilidade leucocitária (HLA) e pênfigo vulgar em pacientes brasileiros." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-21122010-111128/.

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INTRODUÇÃO: O Pênfigo Vulgar é uma doença bolhosa crônica que acomente pele e mucosas. A perda de adesão epitelial ocorre por agressão autoimune às desmogleínas presentes nos desmossomos, mediada por anticorpos IgG. Estudos sobre a gênese da autoimunidade no pênfigo indicam associação entre alelos do sistema HLA, especialmente dos loci DR e DQ. A população brasileira apresenta características favoráveis a estudos exploratórios em genética decorrente de sua origem mista e intensa miscigenação. PACIENTES E MÉTODO: O grupo em estudo incluiu trinta e seis pacientes não consanguíneos com diagnóstico de Pênfigo Vulgar comprovado por imunopatologia provenientes do estado de São Paulo, Brasil. Foram tipados para os loci HLA-A, HLA-B e HLA-DR utilizando-se oligonucleotídeos sequência-específica (PCR-SSO). As frequências alélicas e fenotípicas encontradas foram comparadas com as de um grupo controle composto de dados de 712 indivíduos doadores voluntários cadastrados no Registro Nacional de Doadores de Medula Óssea (REDOME) provenientes de São Paulo e tipados pelo mesmo método. O valor de P crítico foi corrigido utilizando-se o método False Discovery Rate. RESULTADOS: Os alelos HLA-DRB1*04:02, DRB1*08:04 e DRB1*14 estiveram associados à doença com riscos relativos de 44,6, 18,6 e 4,8, respectivamente (p<0,001). Não houve diferença estatisticamente significante entre as frequências de nenhum alelo dos loci HLA-A ou HLA-B entre os grupos. DISCUSSÃO: O alelo DRB1*04:02, diretamente, e o alelo DRB1*14, indiretamente por desequilíbrio de ligação com DQB1*05:03, estão associados com Pênfigo Vulgar em diversas populações ao redor do mundo, porém nenhum estudo semelhante observou associação com o alelo DRB1*08:04 em tamanha magnitude. Acreditamos que as associações encontradas em nosso estudo não sejam decorrentes de viés de estratificação populacional. É necessária, no entanto, a tipagem de loci adjascentes ao HLA-DR dos indivíduos do grupo em estudo para diferenciar se o risco à doença é inerente a estes alelos ou a algum outro nas proximidades, com o qual estariam em desequilíbrio de ligação. CONCLUSÕES: Os alelos HLA-DRB1*04:02, DRB1*08:04 e DRB1*14 estiveram associados ao Pênfigo Vulgar em pacientes brasileiros.
BACKGROUND: Pemphigus vulgaris is a chronic blistering disease affecting skin and mucous membranes. Autoimmune aggression to desmoglein in desmosomes, mediated by IgG antibodies, leads to loss of epithelial cell adhesion. Studies indicate association between some alleles of the HLA system and pemphigus vulgaris, mainly at the DR and DQ loci. Brazilian population characteristics are conducive to genetic exploratory studies because of its various origins and intense ethnically admixture. PATIENTS AND METHODS: The study group consisted of thirty-six unrelated patients with clinical and immunopathological diagnosis of pemphigus vulgaris from a tertiary hospital in Sao Paulo - Brazil. HLA allele typing at the A, B and DR loci was performed after DNA extraction using polymerase chain reaction and sequence-specific oligonucleotide probes (PCR-SSO). Allele and phenotypic frequencies were compared to those from a control group composed by 712 individuals volunteer donors registered in a national registry of bone marrow donors (REDOME) from Sao Paulo, typed using the same method. False Discovery Rate method was used to adjust level of critical P values. RESULTS: The HLADRB1* 04:02, DRB1*08:04 and DRB1*14 were associated with pemphigus vulgaris with relative risks of 44.6, 18.6 and 4.8, respectively (p <0.001). There was no significant difference between the frequencies of any allele of loci HLAA or HLA-B among the groups. DISCUSSION: The alleles DRB1*04:02 and DRB1*14 (indirectly through linkage disequilibrium with the DQB1*05:03) are associated with pemphigus vulgaris in several populations worldwide, however, no similar study reported such magnitude of association between pemphigus vulgaris and DRB1*08:04 allele. We consider that the association is not secondary to population stratification bias. HLA typing of nearby loci is required to differentiate if the association with pemphigus vulgaris is inherent to the HLA-DRB1*08:04 allele or to another gene which is in linkage disequilibrium. CONCLUSIONS: The HLA-DRB1*04:02, DRB1*08:04 and DRB1*14 were associated with pemphigus vulgaris in Brazilian patients

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Silva, Milton Thiago Guerino da. "Avaliação de potencial agente vacinal contra o S.pyogenes em camundongos transgênicos, portadores de genes HLA de classe II humanos." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-20122011-155537/.

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A faringite estreptocócica desencadeada pelo Streptococcus pyogenes pode resultar em uma série de doenças humanas e complicações como a febre reumática (FR) em indivíduos predispostos não tratados. A FR é uma doença autoimune que afeta mais de 20 milhões de crianças em países em desenvolvimento. A proteína M presente na membrana do S. pyogenes representa o maior fator de virulência da bactéria, e é objetivo de estudos para o desenvolvimento de uma vacina contra essa patologia. Atualmente mais de 200 tipos de proteínas M foram descritos na literatura e a sua porção Cterminal é conservada entre os diferentes tipos. Desenvolvemos um protótipo de vacina que compreende 55 resíduos de aminoácido da porção C-terminal, denominado StreptInCor. Neste trabalho analisamos a resposta humoral e celular específica contra o peptídeo sintético StreptInCor, usando camundongos transgênicos portadores de HLA de classe II humanos DR2, DR4, DQ6 e DQ8. O protocolo de imunização consistiu em administrar 50 g do StreptInCor adsorvido em 300 g de hidróxido de alumínio nos dias 0 e 14. Os grupos controles foram injetados com salina nas mesmas condições. O soro obtido no 28º dia foi testado por ensaio imunoenzimático (ELISA) para verificarmos a presença de anticorpos contra o StreptInCor e os esplenócitos destes animais, obtidos nessa data, foram utilizados para ensaios de proliferação celular na presença do StreptInCor. Testes de segurança foram efetuados e não observamos reação cruzada contra a miosina cardíaca e após 12 meses de acompanhamento, amostras de tecidos desses animais foram submetidas à análise histológica. Em conclusão não verificamos indícios de reações autoimunes nos animais imunizados com o StreptInCor e os resultados obtidos mostram a capacidade do StreptInCor em desencadear uma resposta imune, duradoura e segura em camundongos portadores de moléculas HLA de classe II
Streptococcal pharyngitis triggered by Streptococcus pyogenes throat infection can result in rheumatic fever (RF) and rheumatic heart disease (RHD) in untreated susceptible individuals. RF is an autoimmune disease that affects more than 20 million children in developing countries. M protein is the major factor of virulence of the bacteria, and it has been studied to develop a vaccine. Currently more than 200 M protein types have been described and its Cterminal domain is conserved in many different serotypes. We developed a vaccine epitope (StreptInCor) composed by 55 amino acid residues of the Cterminal portion of the M protein. In the present work we analyze the ability of the StreptInCor of induce immune response in HLA class II transgenic mice. The transgenic mice harboring the HLA Class II DR2, DR4, DQ6 and DQ8 were immunized subcutaneously with 50 g StreptInCor adsorbed onto 300 g of aluminum hydroxide gel on days 0 and 14. Control groups were immunized with vehicle (Saline) in same conditions. The sera were obtained on day 28 and tested by ELISA to verify the presence of antibodies. The specific cellular immune response was evaluated by proliferation assay using splenocytes. No cross reaction with cardiac myosin were observed. Tissue samples from immunized mice followed by 12 months were analyzed in order to verify if StreptInCor induces some histological damage. No autoimmune or deleterious reactions were observed. In conclusion our results indicate that StreptInCor Induces a good and prolonged and safe immune response in HLA class II transgenic mice

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Takejima, Priscila Megumi. "Tipificação do HLA nos fenótipos alérgico e não alérgico da asma." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-05102015-111908/.

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A asma é uma doença heterogênea caracterizada por um processo inflamatório crônico das vias aéreas inferiores que está associado ao desenvolvimento da hiperresponsividade brônquica e remodelamento da via aérea. Atualmente, a asma é considerada uma síndrome, ou ao menos uma doença com diversos fenótipos. Tradicionalmente, dois fenótipos são bem definidos pela clínica e exames subsidiários: asma alérgica e asma não alérgica. Eles são diferentes quanto á idade de início, apresentação clínica, história pessoal e familiar de atopia e resposta ao tratamento. Ao contrário da asma alérgica, cuja fisiopatologia está bem caracterizada, a etiologia e mecanismos envolvidos na asma não alérgica não estão bem elucidados. Algumas possibilidades incluem alergia desencadeada por antígenos desconhecidos (fungos), infecção persistente (Chlamydia trachomatis, Mycoplasma sp) e auto-imunidade. Estudos têm descrito em diferentes populações associações entre a asma e alelos/antígenos HLA classe I e II, mas os resultados têm sido inconclusivos. O objetivo deste estudo foi identificar possíveis associações do antígeno leucocitário humano (HLA) classe I (A, B, C) e II (DR, DQ, DP) em pacientes brasileiros com asma alérgica e não alérgica. Um total de 109 pacientes com o diagnóstico de asma (56 com asma alérgica e 53 com asma não alérgica) que estavam em acompanhamento no Serviço de Imunologia Clínica e Alergia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e 297 controles (doadores falecidos de órgãos sólidos) tiveram seu sistema HLA classe I (A, B e C) e II (DR, DQ e DP) tipificado. Os pacientes também realizaram espirometria e coletaram sangue para a quantificação da imunoglobulina E (IgE) sérica total e nível sérico de eosinófilos. Além disso, foram avaliados quanto à IgE específica para aeroalergenos através do teste cutâneo de puntura e a pesquisa da IgE sérica específica (ImmunoCAP). O grupo com asma alérgica foi constituído por pacientes que apresentavam resultado positivo para a pesquisa da IgE específica em ambos teste cutâneo de puntura e na investigação in vitro. E o grupo com asma não alérgica apresentava resultados negativos nos dois testes. A comparação do HLA classe I nos grupos estudados identificou frequência significativamente maior do HLA-B*42 e HLA-C*17 no grupo com asma alérgica, enquanto o HLA-B*48 estava estatisticamente associado com o fenótipo não alérgico. Na análise do HLA classe II, o HLA-DPA1*03 e HLA-DPB1*105 apresentou associação com os pacientes com asma alérgica. Concluindo, o estudo observou diferentes associações dos alelos HLA classe I e II com asma alérgica e não alérgica na população brasileira, a qual é caracterizada pela diversidade de origens e miscigenação. Porém, a predisposição genética para asma é poligênica e novos estudos em grandes populações são necessários para confirmar a associação do HLA como fator protetor ou causador da doença
Asthma is a heterogeneous chronic inflammatory disease of lower airways associated with the development of bronchial hyperresponsiveness and airway remodeling. Currently, asthma is regarded as a syndrome or at least a disease with several phenotypes.Traditionally, two phenotypes of asthma have been defined according to clinical and laboratory features: allergic and non-allergic asthma. Each of them has distint age of onset, clinical presentation, personal and family history of allergy and response to therapy. In contrast to allergic asthma, which pathophysiology is well characterized, the etiology and mechanisms involved in non-allergic asthma remain unclear. Some possibilities include allergy triggered by unknow antigens (fungi), persistent infection (Chlamydia trachomatis, Mycoplasma sp) and autoimmunity. Studies have reported associations between asthma and HLA class I and II alleles/antigens in different populations, but the results have been inconclusive. The objective of this study was to identify possible associations of the human leukocyte antigens (HLA) class I (A, B and C) and II (DR, DQ and DP) in Brazilian patients with allergic and non-allergic asthma. A total of 109 patients with asthma (56 with allergic asthma and 53 with non-allergic asthma), who were being followed at the Service of Clinical Immunology and Allergy of the Hospital das Clínicas of the University of São Paulo Medical School, and 297 controls (deceased solid organ donors) had their HLA class I (A,B and C) and II (DR, DQ and DP) typing. Patients performed spirometry and had their blood drawn to measure total serum immunoglobulin E (IgE) levels and eosinophil count. Furthermore, they were assessed for specific IgE to aeroallergens with skin prick test and serum tests (ImmunoCAP). The allergic asthma group was composed of patient presenting positive results for specific IgE in both skin prick test and in vitro assay. And the non-allergic asthma group had negative results in both tests. There were significantly higher frequencies of HLA-B*42 and HLA-C*17 in the allergic asthma group, whereas the HLA-B*48 was associated with the non-allergic group. Regarding HLA class II analysis, HLA-DPA1*03 and HLA DPB1*105 were associated with allergic asthma patients. In conclusion, the study identified different associations of HLA class I and II with allergic and non-allergic asthma in the Brazilian population, which is characterized by diversity of origins and miscegenation. However, the genetic predisposition of asthma is polygenic and new studies on large populations are needed to confirm the role of HLA as a protective or predisposing factor of disease

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Tavares, Marcos Soares. "Estudo caso-controle da região HLA de pacientes com Granulomatose com poliangeíte." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5150/tde-01032017-134802/.

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Os alelos HLA-DPB1*04 e HLA-DRB1*15 estão fortemente associados à Granulomatose com poliangeíte (GPA). Neste estudo, analisamos se os pacientes brasileiros com diagnóstico de GPA apresentam uma base genética na região HLA. Conduzimos um estudo caso-controle, em que analisamos os alelos da região HLA classe I e II em 55 pacientes com diagnóstico de GPA, atendidos no ambulatório de Vasculites Pulmonares do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e comparamos com os resultados de 110 controles saudáveis. Comparamos também quatro diferentes apresentações clínicas da GPA e a positividade do anticorpo anticitoplasma de neutrófilos (ANCA) com os alelos da região HLA classe I e II. Foi também construída uma árvore de decisões, usando o algoritmo de CART, para a verificação da associação entre os alelos HLA e GPA. Como resultados, observamos que a GPA esteve fortemente associada à presença dos alelos DPB1*04 e DRB1*15 (p = 0,007, odds ratio [OR]: 2,9, 95% intervalo de confiança [IC]: 1,09-3,8; p = 0,006, OR: 2,87, 95% IC: 1,44-4,75, respectivamente) e não à presença do alelo DRB1*04. O alelo DRB1*13 esteve associado com proteção contra GPA (p = 0,042, OR: 0,42, 95% CI: 0,21-0,99). O alelo DPB1*04 esteve significativamente associado a GPA e ANCA-C positivo (OR: 5,47) e à presença de insuficiência renal aguda (p = 0,01037). Concluímos que houve uma interdependência significativa entre os alelos DPB1*0401, DPB1*0402, DRB1*13, C*2 e GPA. Na população estudada, quando o alelo DPB1*04 esteve presente em homozigose, o risco de GPA foi de 81%. Quando o alelo DPB1*0401 esteve ausente ou em heterozigose com o DPB1*0402, como o outro alelo, ou DPB1*0402 esteve em homozigose, o risco da GPA foi de 52,9%. No caso de ausência dos alelos DPB1*0401, DPB1*0402 e DRB1*13, a presença do alelo C*2 aumentou o risco da GPA para 62,5%. Finalmente, na ausência do alelo DPB1*0401 e DPB1*0402 e na presença do alelo DRB1*13, o risco de GPA diminuiu para 0%
The alleles HLA-DPB1*04 and HLA-DRB1*15 are strongly associated with granulomatosis with polyangiitis (GPA). In this study, we examined whether Brazilian patients with GPA had an HLA region genetic background. We conducted a case-control study, in which we analysed alleles of HLA region class I and II from 55 patients with GPA (at the Pulmonary Vasculitis Clinic of the University of São Paulo) and compared the results with those from 110 healthy controls. Comparisons were also performed for 4 different clinical presentations of GPA and anti-neutrophil cytoplasmic antibody (ANCA) positivity and the HLA class I and II region alleles. A tree model decision analysis was conducted using CART algorithm. Our results showed that GPA was strongly associated with alleles DPB1*04 and DRB1*15 (p = 0.007, odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.09-3.8; p = 0.006, OR: 2.87, 95% CI: 1.44-4.75, respectively) and not with the allele DRB1*04. DRB1*13 allele was associated with protection against GPA (p = 0.042, OR: 0.42, 95% CI: 0.21-0.99). DPB1*04 was significantly associated with GPA plus positive C-ANCA (OR: 5.47) and acute renal failure (p = 0.01037). We concluded that there was a significant interdependence among alleles and GPA. In our population, when allele DPB1*04 was presented in homozygous, the risk of GPA was 81%. When DPB1*0401 allele was absent or heterozygous with DPB1*0402 as the other allele, or DPB1*0402 was homozygous, the risk of disease was 52.9%. If DPB1*0401, DPB1*0402, and DRB1*13 were absent, the presence of C*2 increased the risk of GPA to 62.5%. Finally, in the absence of DPB1*0401 and DPB1*0402 and the presence of DRB1*13, the risk of GPA decreased to 0%

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Painter, Corrie A. "Conformational Lability in MHC II Proteins: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/539.

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MHC II proteins are heterodimeric glycoproteins that form complexes with antigenic peptides in order to elicit a CD4+ adaptive immune response. Even though there have been numerous MHC II-peptide crystal structures solved, there is little insight into the dynamic process of peptide loading. Through biochemical and biophysical studies, it has been shown that MHC II adopt multiple conformations throughout the peptide loading process. At least one of these conformations is stabilized by the MHC II-like homologue, HLA-DM. The main focus of this thesis is to elucidate alternate conformers of MHC II in an effort to better understand the structural features that enable HLA-DM catalyzed peptide loading. In this thesis, two altered conformations of HLA-DR were investigated, one modeled in the absence of peptide using molecular dynamics, and one stabilized by the mutation αF54C. The model for the peptide-free form of HLA-DR1 was derived from a molecular dynamics simulation. In this model, part of the alpha-subunit extended-strand region proximal to the peptide binding groove is folded into the peptide-binding groove such that the architecture of the critical peptide binding pocket, P1, as well as the invariant hydrogen bonding network were maintained. Biochemical studies aimed at validating the predicted structural changes were consistent with the model generated from the simulations. Next, structural studies were carried out on an MHC II mutant, αF54C, which was shown to have unique peptide binding characteristics as well as enhanced susceptibility to HLA-DM. Although this mutation did not affect the affinity for peptide, there was a striking increase in the rate of intrinsic peptide release. Both αF54C and αF54A were over 100-fold more susceptible to HLADM catalyzed peptide release than wild type as well as other mutants introduced along the peptide binding groove. In addition, mutation of the αF54 position results in a higher affinity for HLA-DM, which, unlike wild type, is detectable by surface plasmon resonance. Crystallographic studies resulted in a 2.3 Å resolution structure for the αF54C-Clip complex. There were two molecules in the asymmetric unit, one of which had no obvious deviations from other MHC II-pep complexes and one which had a conformational change as a result of a crystal contact on the αF51 residue, a residue which has been shown to be involved in the HLA-DM/HLA-DR binding interface. The crystal structure of wild type HLA-DR1- Clip was also solved, but did not have the altered conformation even though there was a similar crystal contact at the αF51. These data suggest the altered conformation seen in the mutant structure, results from increased lability in the extended stand region due to the αF54C mutation. As a result of this work, we have developed a new mechanistic model for how structural features of MHC II influence DM mediated peptide release.

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Hume, Clifford Robert. "Regulation of HLA class II expression in class II negative mutant B-cell lines /." Access full-text from WCMC, 1989. http://proquest.umi.com/pqdweb?did=745028251&sid=1&Fmt=2&clientId=8424&RQT=309&VName=PQD.

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BIGNON, JEAN-DENIS. "Contribution a l'etude du polymorphisme des genes hla de classe iii par biologie moleculaire." Nantes, 1992. http://www.theses.fr/1992NANTO6VS.

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Muñoz, Torres Pau Marc. "Bioinformatic Study of Antigen Presentation by HLA class II." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/129336.

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Entendre quin és el cribratge al que estan sotmesos els pèptids abans de poder-se unir a les molècules del complex major d’histocompatibilitat classe II o major histocompatibility complex class II en angles (MHC classe II o HLA classe II en humans) per a més tard ser presentats als limfòcits T és especialment rellevant per les seves implicacions en salut, a l’estar involucrats en diferents processos relacionats amb la defensa de l’organisme, des de la resposta davant d’infeccions a les reaccions autoimmunitàries, passant pel reconeixement de les cèl·lules cancerígenes. L’objectiu d’aquesta tesi ha estat desenvolupar diferents estratègies usant tècniques bioinformàtiques per a identificar els patrons que reconeixen les diferents molècules del HLA alhora de seleccionar els pèptids que més tard presentaran els diferents al·lels i, per extensió, poder arribar a predir si un determinat pèptid tindrà la capacitat d’unir-se a una determinada molècula d’HLA. Un cop desenvolupat l’algoritme de determinació i predicció de patrons es va construir una plataforma web per poder-hi analitzar grans quantitats de pèptids i/o proteïnes mitjançant diferents funcionalitats. Per a poder assolir aquests objectius, el treball es va dividir en tres fases diferents. La primera fase va consistir en construir una base de dades relacional en postgesql per a poder-hi emmagatzemar tant la informació requerida per al correcte funcionament de l’algoritme com les dades resultants de l’anàlisi d’aquesta informació. La informació requerida per al correcte funcionament de l’algoritme està formada per epítops per als quals es coneix si són o no presentats per les diferents molècules d’HLA classe II i diferents proteomes de patògens humans, així com el proteoma humà. A més a més, s’hi ha inclòs una secció privada on els usuaris registrats poden pujar-hi dades d’epítops derivades de les seves pròpies investigacions per poder-los analitzar en combinació amb les dades públiques del sistema per a una mateixa molècula. En la segona fase d’aquest treball es varen desenvolupar dos predictors, el primer usant un sistema basat en matrius de puntuació específiques de posició (position-specific scoring matrices en anglès, també conegudes com a PSSM) i el segon usant màquines d’aprenentatge de vectors de suport (Suport vector machines en anglès o SVM). Les PSSM varen ser desenvolupades usant un protocol iteratiu d’optimització, on es comença usant la informació proporcionada per l’alineament de segments de 9 residus en epítops, identificats com a possibles regions d’interacció amb les molècules d’HLA objectes de estudi, i posteriorment es va afegint informació tant de pèptids que no s’uneixen a la molècula com del grau de conservació dels diferents al·lels. Per a la construcció de la SVM, els segments d’unió dels pèptids a cada una de les molècules d’HLA es van definir a partir les PSSM construïdes per a cada una d’elles i els paràmetres per a la SVM amb una funció de base radial (Radial-basis function o RBF) com a nucli (kernel) varen ser fixades individualment per a cada cas a fi i efecte d’assolir els millors resultats possibles. En la tercera i última fase d’aquest projecte, es van construir dos pàgines web, una per cada predictor. Aquests predictors tenen en comú que els usuaris en general poden introduir-hi llistats de pèptids i/o proteïnes en format FASTA per a ser analitzades. Aquestes anàlisi tornen com a resultat els possibles motius d’unió detectats i la seva localització en els proteomes seleccionats. Una característica particular del predictor basat en PSSM és que els usuaris registrats poden pujar seqüències resultants de la seva pròpia investigació per trobar nous patrons d’unió a molècules d’HLA noves o millorar els existents i fer prediccions amb ells.
Understanding how peptides are selectively bound and presented by major histocompatibility complex class II molecules (MHC class II or HLA class II in humans) is of outmost importance for its broad implications in human health, from infection to autoimmunity or cancer. The aim of this thesis was to develop a computational strategy to identify HLA class II binding patterns for a variety of alleles and use this knowledge to predict their capacity to bind specific peptide sequences. To make an effective use of the prediction algorithm, a web-based platform for the analysis of large peptide or protein sets, including various functionalities, was also devised. In order to accomplish these objectives, the work was divided into three different stages. The first stage consisted in the construction of a postgresql relational database to store all the information required for and generated by the algorithms developed. The required, uploaded information (subject to updates) consisted of known HLA class II epitopes and the translated genomes of a list of pathogenic bacterial species and human. In addition, the database was designed to include a private section for the upload of user-owned epitope information, which the owner may use in combination with the public data. In a second stage two predictors were developed, one using position-specific scoring matrices (PSSMs) and the other one using a support vector machine (SVM). PSSM development was performed using an iterative optimisation protocol, starting from the alignment of known epitopes to identify HLA class II binding cores (9-residue segments) and incorporating additional information such as allele conservation and non-binders at different phases of the refinement. For SVM construction, the epitope core was defined using the corresponding PSSM and the parameters for the SVM with a radial-basis-function (RBF) kernel were set up individually for each molecule to get the best performance. In the third stage, two web pages were constructed, one for each predictor. The servers share a common part in which the user can introduce peptide or protein sequences in Fasta format to perform an analysis that delivers both putative epitopes and their localization in a selected proteome. In addition, the PSSM-based server allows the user to upload his/her own sequences to elucidate new HLA class II binding patterns and perform predictions with them.

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Scriba, Thomas Jens. "HIV T helper immunity studied with HLA class II tetramers." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425908.

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L'HEVEDER, MARIE-CECILE. "Etude des genes du systeme hla de classe ii dans le terrain genetique et l'expression clinique de la polyarthrite rhumatoide." Rennes 1, 1994. http://www.theses.fr/1994REN1M118.

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DELLALIBERA, Edileine. "Polimorfismo de genes de HLA classe II (DRB1, DQA1 e DQB1) e associação com doenças parasitárias na população do Estado de Pernambuco." Universidade Federal de Pernambuco, 2004. https://repositorio.ufpe.br/handle/123456789/2190.

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A população da Região Nordeste do Brasil originou-se a partir da miscigenação entre caucasianos europeus, negros africanos e índios nativos. Entretanto, apesar dos vários estudos realizados com populações brasileiras, pouco se sabe sobre a contribuição de cada um dos grupos étnicos na formação da atual população nordestina inferida pelo polimorfismo dos locos de HLA. No presente estudo uma amostra da população do Estado de Pernambuco foi caracterizada quanto ao polimorfismo dos locos de HLA-DRB1, -DQA1 e -DQB1 e verificadas possíveis associações dos locos DRB1 e DQB1 com filariose bancroftiana e do loco DQB1 com esquistossomose mansônica na mesma população. Os alelos DRB1*0701 (0,1390), DQA1*0102 (0,1954) e DQB1*0201 (0,2128) foram os mais freqüentemente encontrados nesta população. Foram identificados no total 113 possíveis haplótipos, sendo o DRB1*0701-DQA1*0201-DQB1*0201 (0,1234) o mais freqüente na população pernambucana. Os resultados mostraram que a população pernambucana está geneticamente mais próxima de populações caucasianas européias e mais distante de negros africanos e índios nativos, embora tenham sido encontrados nela alelos típicos de populações indígenas e alelos característicos de populações africanas. Não foi encontrada nenhuma associação entre o loco HLA-DQB1 e esquistossomose mansônica na população estudada. Foram encontradas associações de susceptibilidade, conferida pelos alelos DRB1*0301 e DQB1*0402, e de proteção, conferida pelos alelos DRB1*0102, DQB1*0401 e DQB1*0608, ao desenvolvimento da filariose bancroftiana na população do Estado de Pernambuco

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Camargo, Ana Vitória da Silveira. "Genes HLA de classe II (DRB1 e DQB1) como fatores de risco para a toxoplasmose ocular." Faculdade de Medicina de São José do Rio Preto, 2016. http://hdl.handle.net/tede/377.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP
Introduction: Toxoplasmosis, a disease resulting from Toxoplasma gondii infection, is clinically manifested through ocular, cerebral and congenital ways. This pararsito Apicomplexa is capable of infecting cells of all nucleated tissues and may remain in a latent state or cause irreversible cell damage. The HLA class II genes control the adaptive immune response humoral and influence susceptibility and the resistance to infectious and parasitic diseases. The ocular toxoplasmosis, besides being dependent on infection with T. gondii as well as the variability of the infecting strain, is influenced by host genetic factors. Aim: To test the hypothesis that the HLA class II genes (HLA-DRB1 and HLA-DQB1) are associated with ocular toxoplasmosis. Materials and Methods: Samples of 249 patients undergoing ophthalmologic evaluation and positive serology to T. gondii were analyzed. According to the clinical conditions, two distinct groups were composed: one formed by patients with ocular toxoplasmosis (n=123); and another group with patients without the disease ocular form (n=126). The patients with ocular toxoplasmosis were subdivided into two groups, according to the type of ocular manifestation: primary (n=93 samples) or recurrent (n=30). Genotyping of Class II HLA alleles were performed by the polymerase chain reaction technique with specific oligonucleotide sequence (PCR-SSO; One Lambda®). Results: The average ages of the group of patients with ocular toxoplasmosis was less (40.9±19.9) than the average age of patients without ocular toxoplasmosis (57.6±17.2) (p<0.0001).The alleles HLA-DRB1*03 (OR=1,94; IC 95% 1.09-3.45; p=0.031; pc=0.404) and HLA-DQB1*02 (OR=1.52; IC 95% 1.03-2.24; p=0.039; pc=0.197) showed a more allelic frequency in patients without ocular toxoplasmosis when compared to the group with ocular toxoplasmosis. The HLA-DRB1*14 alelle was more frequent in the subgroup of the recurrent manifestation, when compared to the group without ocular toxoplasmosis (OR=0.32; IC 95% 0.12-0.83; p=0.032; pc=0.417) and to the primary manifestation subgroup (OR=0.25; IC95% 0.08-0.73; p=0.017; pc=0.223). The HLA-DRB1*03_DQB1*02 haplotype was not associated with the lower risk of ocular toxoplasmosis (OR=1.86; IC 95%: 1.03-3.36; p=0.052). Conclusions: The obtained results suggest that the Class II HLA genes (DRB1 and DQB1) are not associated with the ocular toxoplasmosis development; and that none HLA DRB1_DQB1 haplotype influences the ocular toxoplasmosis development in the study population.
Introdução: A toxoplasmose, uma doença resultante da infecção por Toxoplasma gondii, manifesta-se clinicamente nas formas ocular, cerebral e congênita. Este parasito Apicomplexa infecta células nucleadas de todos os tecidos e pode permanecer em estado latente ou provocar danos celulares irreversíveis. Os genes HLA de classe II controlam a resposta imune adaptativa humoral e influenciam a suscetibilidade e a resistência às doenças infecciosas e parasitárias. A toxoplasmose ocular, além de ser dependente da infecção por T. gondii e da variabilidade das cepas infectantes, é fortemente influenciada por fatores genéticos do hospedeiro. Objetivo: Testar a hipótese de que os genes HLA de classe II (HLA-DRB1 e HLA-DQB1) estão associados à toxoplasmose ocular. Materiais e Métodos: Foram analisadas amostras de DNA de 249 indivíduos submetidos à avaliação oftalmológica e com sorologia reagente para T. gondii. De acordo como quadro clínico, dois grupos distintos foram compostos: um formado por pacientes com toxoplasmose ocular (n=123) e outro grupo, por pacientes sem a forma ocular da doença (n=126). Os pacientes com toxoplasmose ocular foram subdivididos em dois grupos de acordo com o tipo de manifestação ocular: primária (n=93) ou recorrente (n=30). A genotipagem dos alelos HLA de classe II foi realizada pela técnica reação da cadeia de polimerase com sequência de oligonucleotídeos específicos (PCR-SSO; One Lambda®). Resultados: A média de idade dos pacientes com toxoplasmose ocular foi menor (40.9±19.9) que a daqueles sem toxoplasmose ocular (57.6±17.2) (p<0.0001). Os alelos HLA-DRB1*03 (OR=1,94; IC 95% 1.09-3.45; p=0.031; pc=0.404) e HLA-DQB1*02 (OR=1.52; IC 95% 1.03-2.24; p=0.039; pc=0.197) apresentaram maior frequência alélica no grupo sem toxoplasmose ocular em comparação ao grupo com toxoplasmose ocular. O alelo HLA-DRB1*14 foi mais frequente no subgrupo com a manifestação recorrente em comparação ao grupo sem toxoplasmose ocular (OR=0.32; IC 95% 0.12-0.83; p=0.032; pc=0.417) e com o subgrupo manifestação primária (OR=0.25; IC95% 0.08-0.73; p=0.017; pc=0.223). O haplótipo HLA-DRB1*03_DQB1*02 não se mostrou associado ao menor risco de toxoplasmose ocular (OR=1.86; IC 95%: 1.03-3.36; p=0.052). Conclusões: Os resultados obtidos sugerem que os genes HLA de classe II (DRB1 e DQB1) não estão associados com o desenvolvimento da toxoplasmose ocular e que nenhum haplótipo HLA DRB1_DQB1 influencia o desenvolvimento desta doença na população analisada.

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GU, XUE FAN. "Marqueurs genetiques du diabete de type 1 : analyse du polymorphisme des genes hla de classe ii." Paris 6, 1991. http://www.theses.fr/1991PA066143.

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Le diabete insulino-dependant (did) est une maladie auto-immune, qui se developpe sur un terrain genetique particulier. En utilisant les techniques de pcr, de slot blot, de cartographie de restriction et de sequencage nucleotidique, nous avons caracterise les exons 2 des loci hla-dqb1, dqa1 et des sous-types de dr4 chez 157 diabetiques et chez 147 temoins. Le profil genetique de hla-dqb1 chez les did presente un gradient susceptibilite/resistance au did selon les combinaisons alleliques presentees. La nature des codons dq 57 et dq 52 est importante. Les heterozygoties dqb1*0201/0302 et dqa1*0301/0501 sont enrichies chez les did. Environ 50% des did portent un profil particulier (dqb1 asp 57 /, dqa1 arg 52 +/+). Surtout 28% des did presentent une combinaison haplotypique (dqb1*0201/0302, dqa1*0301/0501) qui n'a pas ete retrouvee chez les temoins avec le risque relatif le plus eleve (o. R. =83). Le profil genetique de hla-dq est identique chez les deux types de did de type ia et ib. Les etudes de hla-dq chez les francais et les algeriens montrent que ces deux populations presentent un profil presque identique. L'etude des sous-types de hla-dr4 montre que c'est le locus dqb1 et non drb1 qui est le plus proche du locus diabetogene. Ces resultats ont une valeur theorique pour l'immunogenetique du did. Ils ont une valeur pratique pour les campagnes de depistage

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Hiwa, Ryosuke. "Myeloperoxidase/HLA class II complexes recognized by autoantibodies in microscopic polyangiitis." Kyoto University, 2017. http://hdl.handle.net/2433/228231.

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19

Gruneberg, Ulrike. "The interaction of HLA-DM with conventional MHC class II molecules." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322410.

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Sturniolo, Tiziana Concetta. "Systematic characterisation of HLA Class II ligand binding specificity by quantitative matrices." Thesis, Open University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264399.

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Chou, Chih-Ling. "Defining the mechanism of MHC class II peptide editing by HLA-DM." Available to US Hopkins community, 2003. http://wwwlib.umi.com/dissertations/dlnow/3080640.

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Zavala-Ruiz, Zarixia 1977. "Structure studies of the human class II major histocompatibility complex protein HLA-DR1." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17842.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.
Vita.
Includes bibliographical references (leaves 149-162).
Major Histocompatibility Complex (MHC) proteins are heterodimeric membrane glycoproteins that bind antigens in the form of short peptides within the cell and present them to the T cell receptors on the surface T cells. In this thesis work, the structural aspects of the human class II MHC protein HLA-DR1 in complex with different peptides and also in the peptide-free form were investigated. Biochemical, crystallographic, and immunological analyses of an unusually long peptide antigen derived from HIV-gag (p24) and its interaction with HLA-DR1 and a HIV-specific CD4+ T cell clone were studied. The HIV-gag (p24) peptide binds in an unexpected conformation, with its C- terminal region making a hairpin turn that bends back over the groove. The residues at the C-terminus are critical for T-cell recognition, and disruption of the hairpin turn abrogates the immune response. The results suggest a new mode of MHC-peptide-TCR interaction. A set of viral peptide analogs designed to increase binding affinity for HLA-DR while maintaining antigenic interactions with a virus-specific T cell receptor were designed, tested and analyzed. Ultimately, a N-methyl substitution at position 7 is shown to increase binding affinity by displacement of one of three water molecules bound between the MHC and peptide. The results have implications for design of peptido-mimetic vaccines, and are discussed in the broad context of other attempts to increase protein-ligand interaction through displacement of tightly bound water molecules. The role for the P10 shelf in peptide binding site was investigated. Crystallographic studies confirm the formation of a P10 shelf that is lined with highly polymorphic residues. Biochemical studies were conducted
(cont.) on a series of peptides different at the P10 position on four HLA-DRl(P10) mutants showing that this shelf has some specificity and can be involved in the discrimination of peptides that bind to class II MHC proteins. Studies of the empty, peptide-free form of HLA-DR1 were conducted by NMR spectroscopy showing that the conformation of this empty form is not in a molten globule-like state and that in general is similar to that of the peptide-loaded form but with several differences. Preliminary characterization of the peptide-receptive and peptide-averse forms of the empty HLA-DR1 is described.
by Zarixia Zavala-Ruiz.
Ph.D.

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23

Dintwe, One Bridget. "Characterisation of Mycobacterium tuberculosis specific T cell immunity with HLA class II tetramers." Doctoral thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/8713.

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Includes bibliographical references.
Tuberculosis (TB) remains a global health burden, with an estimated 1.3 million people dying from the disease in 2012. Protective immunity against TB is thought to depend on specific T cells. However, exactly which T cell characteristics are required for immunological protection is unknown. To gain a better understanding of M. tuberculosis (M.tb)-specific memory T cell immunity, we studied longevity and function of M.tb-specific memory T cells. We reasoned that such knowledge would facilitate rational vaccine design of a TB vaccine. We designed and developed a set of new HLA class II tetramers to perform in-depth studies of M.tb-specific CD4 T cell responses. We studied persons vaccinated with a novel TB vaccine, MVA85A, as well as persons naturally infected with M.tb. Antigen-specific CD4 T cells were detected with HLA class II tetramers and functional and phenotypic attributes of these T lymphocytes characterised by standard flow cytometric techniques. Comprehensive transcriptional analyses of M.tb-specific CD4 T cells, which were also sorted by FACS, were performed by microfluidic quantitative real-time PCR. Early after intradermal vaccination with MVA85A a large proportion of Ag85Aspecific CD4 T cells were highly activated, expressed skin homing markers and displayed an effector T cell phenotype. This effector response waned rapidly and gave way to antigen-specific central memory CD4 T cells with high proliferative potential, which we proposed may be desirable for protection. However, recent results from the first efficacy trial of MVA85A in infants suggested that these cells are not sufficient to enhance protection beyond that induced by BCG vaccination at birth. Further, we characterised surface marker expression and transcriptional signatures of a newly detected and described population of M.tb-specific CD4 T cells, that displayed a CD45RA+CCR7+CD27+ naÃ¯ve-like T cell phenotype. We hypothesised that these unique M.tb-specific naÃ¯ve-like CD4 T cells had a transcriptional profile distinct from truly naÃ¯ve, central memory and effector bulk CD4 T cells, as well as other M.tb-specific memory CD4 T cell subsets. Gene expression of CFP10-specific naÃ¯ve-like CD4 T cells reflected an mRNA profile that was very distinct from truly naÃ¯ve bulk CD4 T cells. Rather, naÃ¯velike CD4 T cells clustered with bulk effector CD4 T cells in unsupervised analysis methods such as hierarchical clustering and principle component analyses. Further analyses revealed that naÃ¯ve-like CFP10-specific CD4 cells expressed mRNAs coding for effector cytokines, cytotoxic molecules and chemokine receptors consistent with effector memory T cells. However, the overall transcriptional profile was more similar to CFP10-specific central memory CD4 T cells than that of the effector CD4 T cells. We concluded that M.tb-specific naÃ¯ve-like CD4 T cells may possess an ability to traffic to sites of infection or inflammation, where they may contribute to effector function. These hypotheses need confirmation on a protein level. The HLA class II tetramers developed in this thesis are valuabe tools for assessing direct ex vivo M.tb-specific CD4 T cell responses without activation and cell perturbation. Our findings contribute to a more comprehensive understanding of T cell immunity induced by vaccines and/or natural M.tb infection.

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Al-Daccak, Reem. "Etude de la variabilite des genes hla-classe ii : relation phenotype-genotype et application a la greffe de moelle." Paris 7, 1990. http://www.theses.fr/1990PA077235.

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Le polymorphisme hla-classe ii, sa definition au niveau genomique et son importance fonctionnelle constituent les objectifs de ce travail. L'etude du polymorphisme de taille des fragments de restriction (rflp) a montre que la technologie rflp permettait de caracteriser la majorite des alleles hla-dr, dq et dp. Une autre methode de biologie moleculaire (pcr-rflp) plus rapide, plus precise et non radioactive est presentee dans ce travail. Elle est basee sur la caracterisation des fragments de restriction apres amplification de l'exon le plus polymorphe des genes. Cette technique a permis une etude de la molecule hla-dp dans la population caucasoide c'est-a-dire frequence des differents alleles, association des genes dpa et dpb. Notre travail a montre que les rflp, bien qu'etant un typage au niveau genomique, permettent de predire dans la majorite (95,23%) des cas les resultats des reactions lymphocytaires mixtes. Elle a egalement montre la capacite de la molecule hla-dp de provoquer une proliferation au cours d'une mlr primaire. Neanmoins, certaines incompatibilites hla-classe ii ne provoquent pas de proliferation en mlr malgre les differences dans leur sequence primaire. Cela suggere que le polymorphisme dans certains cas est non-fonctionnel dans les reactions allogeniques in vitro. L'evaluation de la compatibilite hla-classe ii dans les greffes de moelle entre germains hla-identiques montre que en face de l'identite genetique hla-dr, dq l'incompatibilite hla-dp entre donneur et receveur ne semble pas jouer un role important sur l'evolution de ce type de greffe. Par contre cette molecule semble importante dans les greffes de moelle non-apparentees, bien qu'une correlation significative entre la maladie du greffon contre l'hote et les incompatibilites hla-dp n'ai pas pu etre mise en evidence du fait du nombre trop faible de cas etudies. Quoi qu'il en soit, les techniques developpees dans ce travail ont apporte beaucoup aux greffes de moelle entre sujets non-apparentes en permettant le choix du donneur le plus identique au receveur

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Standring, Peter. "Class II Human Leukocyte Antigen gene polymorphisms, cell surface expression and immunoglobulin E mediated disease." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262910.

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葉德俊 and Tak-chun Timothy Yip. "Characterization of a monoclonal antibody reactive against major histocompatibility complex class II antigens." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1992. http://hub.hku.hk/bib/B3123334X.

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Yip, Tak-chun Timothy. "Characterization of a monoclonal antibody reactive against major histocompatibility complex class II antigens /." [Hong Kong] : University of Hong Kong, 1992. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13478771.

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McFarland, Benjamin James. "Dissecting the cooperative energetics of the binding interactions between peptides and MHC class II proteins /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/8540.

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Sacramento, Thaiana de Oliveira. "Estudo de associação entre esclerose múltipla , HLA-DRB1* e níveis séricos de IgG em uma população miscigenada de Salvador,Ba." Instituto de Ciências da Saúde, Universidade Federal da Bahia, 2016. http://repositorio.ufba.br/ri/handle/ri/22572.

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A esclerose múltipla é uma doença que afeta preferencialmente o sistema nervoso central de mulheres jovens, causando-lhes graus variáveis de incapacidades física e cognitiva. Etiologicamente associa fatores ambientais, biológicos, sócioeconômicos e genéticos, como por exemplo genes do MHC classe II, especialmente os alelos HLADRB1* 15. Seu diagnóstico é bastante difícil, mas níveis solúveis de IgG podem sugerir atividade da doença. Objetivo:Determinar a frequência dos alelos HLA DRB1* na população baiana em geral e em portadores de esclerose múltipla atendidos no centro de referência do CHUPES, UFBA, no período de outubro de 2014 a abril de 2015 e associá-las aos níveis séricos de IgG. Metodologia: Estudo do tipo caso-controle, aprovado pelo comitê de ética da Faculdade de medicina da Universidade Federal da Bahia (CAAE: 3517134.0.0000.5577), que envolveu uma amostra de conveniência composta por 197 indivíduos, cujos dados sócioclínico-demográficos foram coletados através de questionário desenvolvido para a pesquisa. A genotipagem dos alelos HLADRB1* foi realizada através da técnica “HLA-DR SSO Genotyping Test” e a determinação dos níveis séricos de IgG por nefelometria. Resultados: A análise quantitativa revelou um perfil genotípico do tipo HLA-DRB1*15 (20,5%) em mulheres (83,0%) das raças negra ou parda (75,0%), com faixa etária entre 30 e 39 anos (28,0%), que desenvolveram a forma surtorremissiva da doença (76,0%), nas fases mais avançadas da vida (55,0%), sem permanência de sequela clínica (70,0%) e que usavam algum tipo de Interferon (58,0%). O IgG sérico para o grupo de doentes alcançou valor médio de 1.410 ± 323 mg/dL, e nos controles, esta média foi de 1.532 ± 310 mg/dL. A análise qualitativa indicou maiores frequências, nas formas progressivas de esclerose múltipla dos grupos alélicos HLA-DRB1*12 (22,0%), e dos alelos HLA-DRB1*13 (12,6%) e HLA-DRB1*15 (22,0%) naqueles indivíduos com a forma surto-remissiva. Negros e pardos demonstraram maior prevalência do alelo HLA-DRB1*15 (24,0%), enquanto que nos brancos maior frequência do alelo HLA-DRB1*07 (20,0%) foi encontrada. Negros e pardos portadores da doença tenderam a apresentar maiores níveis séricos médios de IgG (25,4%). Conclusão: Houve forte associação entre as frequências alélicas encontradas e as variáveis raça/etnia e forma clínica da doença. Nesta população, os níveis séricos de IgG não parecem servir como marcadores de progressividade.

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Blötz, Andrea [Verfasser]. "HLA class II mismatch alleles as targets of the alloreactive CD4 T-cell response / Andrea Blötz." Mainz : Universitätsbibliothek Mainz, 2013. http://d-nb.info/1033734268/34.

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Schor, Doris. "Estudo da influência dos alelos do HLA classe I e II e do polimorfismo dos genes de citocinas na infecção pelo HTLV-1." reponame:Repositório Institucional da FIOCRUZ, 2013. https://www.arca.fiocruz.br/handle/icict/14385.

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Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil
INTRODUÇÃO: O vírus linfotrópico para células T humanas (HTLV-1) é o principal agente causador da Paraparesia Espástica Tropical / Mielopatia associada ao HTLV-1 (PET/MAH) e da Leucemia da célula T do Adulto (LTA). A maioria dos indivíduos infectados permanece assintomática, somente 2 a 5% irão desenvolver uma das duas doenças. Fatores da interação HTLV-1/ hospedeiro estão envolvidos no risco de desenvolver doença. A lesão neurológica na PET/MAH parece ser consequência de uma reação inflamatória, desencadeada pelo reconhecimento de células infectadas por linfócitos T citotóxicos, com consequente liberação de citocinas e lesão medular. OBJETIVO: Identificar marcadores genéticos, que possam ajudar no prognóstico e tratamento dos pacientes portadores do HTLV-1. MÉTODOS: Nas amostras de 117 portadores do HTLV-1 assintomáticos e 171 pacientes com acometimento neurológico em acompanhamento na cidade do Rio de Janeiro, foram realizadas as tipificações dos genes do HLA Classe I e II, dos polimorfismos dos genes das citocinas -308TNF-\03B1,-174IL-6, +874IFN-\03B3, códon 10 e 25TGF-\03B21 e -1082 - 819-592IL-10, e a quantificação da carga proviral. Os dados foram organizados em um banco de dados no programa SPSS. As frequências alélicas e genotípicas foram obtidas por contagem direta. O equilíbrio de Hardy-Weinberg foi avaliado para os polimorfismos das citocinas no sitio http://bioinfo.iconcologia.net/ubbweb/SNPStats_web, em relação ao HLA foram utilizadas as ferramentas disponíveis no sítio \201CLos Alamos HIV database tools\201D. As comparações entre os grupos foram realizadas através de tabelas de contingência 2x2 (quiquadrado, exato de Fisher e odds ratios), valores de p\22640,05 foram considerados significantes RESULTADOS E CONCLUSÕES: O alelo A*02 não influencia a condição clínica nem os níveis da carga proviral. Os alelos A*29 e B*44 foram mais frequentes entre os indivíduos assintomáticos e a sua presença influenciou os níveis da carga proviral sugerindo proteção ao desenvolvimento de doença neurológica. O alelo A*68 foi mais frequente entre os pacientes com doença neurológica, porém sua presença não influenciou nos níveis da carga proviral. O alelo C*04 foi mais frequente entre os portadores assintomáticos e não influenciou os níveis de carga proviral, já o alelo DRB1*03 predominou entre os pacientes com doença neurológica e a sua presença entre os indivíduos assintomáticos acarretou níveis mais elevados de carga proviral, sugerindo ser um possível fator de risco para o desenvolvimento de doença neurológica. Na análise do polimorfismo genético das citocinas, o polimorfismo de IL-10, com perfil fenotípico de baixo produtor da citocina foi mais frequente no grupo dos assintomáticos, enquanto que o fenótipo de produtor intermediário predominou entre os sintomáticos. O perfil fenotípico da população estudada foi caracterizado como: baixo produtor da citocina -308TNF-\03B1, intermediário a alto produtor para códon 10 e códon 25 TGF-\03B2, baixo a intermediário produtor para -1082,-819,- 592 IL-10, alto produtor para -174 IL-6 e baixo a intermediário produtor para +874IFN-\03B3
INTRODUCTION: The human T cell lymphotropic vírus (HTLV-1) is the main causing agent of Tropical Spastic Paraparesis/HTLV -1 Associated Myelopathy (HAM/TSP) as well as of Adult T Cell Leukemia (ATL). Most of the infected individuals remain asymptomatic, only 2 to 5 % end up developing either one of these diseases. Factors related to the HTLV-1/host interaction may be involved in the risk of developing the diseases. The neurological lesion in HA M/TSP may be the consequence of an inflammatory reaction, triggered by the rec ognition of infected cells by cytotoxic T lymphocytes, followed by the release of cyt okines and central nervous system lesion. OBJECTIVE: This work aims to identif y genetic markers, which may help in the prognosis and treatment of HT LV-1 patients. Methods: Th e polymorphism of the HLA Class I and II genes, as well as the TNF- α , IL6, IFN- γ , TGF- β and IL-10 cytokine genes, and the proviral load were analysed in 117 asymptomatic HTLV-1 carriers and 171 HTLV-1 symptomatic carriers from Rio de Janeiro city. Data were organized into a database using SPSS. The Hardy- Weinberg equilibrium was evaluated for cytokine polimorphisms using the site http ://bioinfo.iconcologi a.net/ubbweb/SNPStats _web. The tools available in the site “Los Alamos HIV dat abase tools” were used to analyze the HLA polimorphism s. Comparisons between groups were made using 2x2 contingency tables (Fisher Exact test/ χ 2 and odds ratios), p values p ≤ 0,05 were considered significan t. RESULTS and CONCLUSIONS: The A*02 allele does not influence the clinical condition or the leve ls of proviral load. The alleles A*29 and B*44 were more frequent among asymptom atic individuals and their presence influenced the levels of prov iral load, suggesting protec tion for the development of neurological disease. The A*68 allele was more frequent among patients with neurological disease, but did not influence the levels of proviral lo ad. The C*04 allele presented a higher frequency in the asymptomatic carriers , and did not influence the proviral load levels. The DRB1*03 allele was more frequent among the symptomatic carriers. However the asymptomatic indi viduals that possess the DRB1*03 allele, have higher levels of proviral load, sugges ting a possible risk factor for neurological disease. In the analysis of the genetic polymorphism of the cytokines, the IL-10 polymorphism, with a phenotypic profile of low cy tokine production was more frequent in the asymptomatic group, while the interm ediate producer phenotype predominated among the symptom atic. The phenotypic profile of the study population was characterized as low cytokine producer 308TNF- α -, intermediate to high producer for codon 10 and codon 25 TGF- β , low to intermediate producer to -1082, - 819, -592 IL-10, high producer for -174 IL-6 and low to intermediate producer to +874 IFN- γ .

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Clay, Timothy Mark. "The role of DNA typing in selecting HLA class II matched unrelated donors for bone marrow transplantation." Thesis, University of the West of England, Bristol, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292211.

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Murthy, Venkatesh Locharla. "Three dimensional structure of a human Class II MHC protein HLA-DR1 bound to an endogenous peptide." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/10561.

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Odunsi, Adekunle Omatayo. "Immunogenetic analysis of HLA Class II in premalignant disease of the cervix and correlation with HPV status." Thesis, Open University, 1999. http://oro.open.ac.uk/54556/.

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The human papilloma virus (HPY) infection has a causal association with cervical intraepithelial neoplasia (CIN) and cervical cancer. However, pre-malignant or malignant transformation is not always observed with HPY infection. lILA molecules are important in the regulation of the immune response to foreign antigens. The role of genetic variation at the HLA class II loci (DR and DQ) in CIN was investigated in 176 British Caucasian patients and 420 controls (normal cervical cytology and negative for HPY 16, 18, 31 and 33). HLA DQB 1 *03 typing was performed by a novel polymerase chain reactionrestriction fragment length polymorphism method (A-RFLP). The technique uses PCR to mutate the first base of codon 40 (DQ alleles) from T to G to create an artificial restriction site for an enzyme, MluI, which distinguishes DQB 1 *03 from other alleles and is confirmed by digestion of amplified DNA with Mlul. Further HLA DR-DQ typing was performed by PCR DNA amplification and oligonucleotide probe typing. HPY types (16, 18, 31 & 33) were detected by using type-specific oligonucleotide primers and PCR. The alleles of the DQB 1 *03, DRB 1 *04 and DRB 1 * 11 groups were strongly associated with susceptibility to CIN. Specifically the haplotypes DRB 1 *040 I-DQB 1 *0301 and DRBl*1101-DQB1*0301 were significant and indicated susceptibility. The DQBl*03 locus was more contributory to this association than the DRB 1 loci. A weak protective effect was shown for the haplotype DRB 1 *0 10 I-DQB 1 *0501. Positive correlation was also observed for HPY-positive CIN, suggesting that specific HLA alleles may be important in determining the immune response to HPY antigens and the risk for CIN after HPY infection. Immunoaffinity purification of the susceptibility and protective HLA ~ molecules was performed and the naturally processed peptides were eluted and sequenced by Edman degradation. The data obtained was used for motif prediction of HPY 16 E6, E7, Ll and L2 sequences that may be capable of binding to these HLA molecules. Motif prediction as well as the binding affinity of predicted peptide motifs for HLA D RB 1 *0401 and DRB 1 *0 10 1 was accomplished using the published data' on the naturally bound peptide sequences bound to these HLA molecules. The results revealed significant differences in both the number and binding affinity of the HPV 16 derived peptides to the protective and susceptibility HLA molecules. These results should help in the rational design of vaccines against HPV.

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Rayner, Michelle Louise. "The role of polymorphic amino acid residues of HLA class II molecules in susceptibility to type 1A diabetes." Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274361.

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Ponte, MauriclÃcio Franco. "Association of HLA CLASS II alleles (DRB1 and DQB1) with clinical features and hematological parameters in sickle cell anemia." Universidade Federal do CearÃ, 2014. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16555.

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Sickle cell anemia (SCA) is an inherited disease, often, but not exclusively, in individuals of African origin. In the black Brazilian population there is a prevalence from 0.1 to 0.3% tending to affect an ever larger portions due to miscegenation. Specific alleles of the HLA system and may influence the risk of appearance of clinical symptoms in patients with SCA, whereas their genotypes may serve as useful markers in identifying the risk for certain clinical manifestations. The study was a randomized-case control in order to evaluate the association of alleles of the HLA class II system with clinical features and hematological parameters of patients with SCA. The genotyping were performed for the DRB1 and DQB1 loci from 62 individuals diagnosed with SCA and 86 healthy individuals (HbA2) used as controls. Allele frequencies (Fa) were obtained by direct counting and calculated by the formula Fa = a / 2n. In the group with SCA the five most common HLA-DRB1 alleles were DRB1*04 (16.9%), DRB1*01 (12.9%), DRB1 * 08 (12.1%), DRB1 * 07 and DRB1 * 11 (both 11.3%), which represent 64.5% of the total variability of the 13 analyzed specificities. The three most frequent alleles were HLA-DQB1 DQB1*03 (45.2%), DQB1*05 (18.5%) and DQB1*06 (16.9%), corresponding to 80.6% of the total variability of the 5 analyzed specificities. For the control group the five most frequent HLA-DRB1 alleles were DRB1*04 (16.3%), DRB1*13 (15.1%), DRB1*08 and DRB1*15 (both 11.6%) and DRB1*07 (8.1%), which represent 62.7% of the total variability of the 13 analyzed specificities. The HLA-DQB1, the three most frequent alleles were DQB1*03 (32.0%), DQB1*06 (22.7%) and DQB1 *05 (19.2%), corresponding to 73.9% of the total variability of the 5 analyzed specificities. Regarding cerebrovascular accident (CVA), the DRB1*15 and DQB1*06 (p = 0.0033 and p = 0.0077, respectively) showed a high frequency in patients who developed stroke. For acute chest syndrome (STA), the DRB1*01 (p = 0.0398) and DQB1*06 (p = 0.0057) were the most frequent allele in the group STA, while the DRB 1*01 alleles (p = 0.03980) and DQB1 * 05 (p = 0.0446) were more frequent in patients without STA. There were no significant associations with painful vaso-occlusive crises. Total hemoglobin and hematocrit (p = 0.045 and 0.0036, respectively), and fetal hemoglobin (HbF) (p = 0.024) were the only hematological parameters that had significant association with the DQB1 locus being responsible for this association. Regarding HbF, the DQ02 and DQ06 alleles were associated with lower and higher levels, respectively, of this hemoglobin fraction in the patients studied (p = 0.015). Our results provide the first evidence that the HLA genes are involved in modification of the clinical course or onset of complications in individuals with SCA in Brazil.
A anemia falciforme (AF) Ã uma doenÃa hereditÃria, frequente, mas nÃo exclusiva, em indivÃduos de origem africana. Na populaÃÃo negra brasileira hÃ uma prevalÃncia de 0,1 a 0,3% tendendo a atingir parcelas cada vez maiores devido Ã miscigenaÃÃo. Alelos especÃficos do sistema HLA e seus haplÃtipos podem influenciar o risco de surgimento de manifestaÃÃes clÃnicas em pacientes com AF, ao passo que os seus genÃtipos podem atuar como marcadores Ãteis na identificaÃÃo do risco para determinadas manifestaÃÃes clÃnicas. O estudo foi do caso-controle randomizado, com o intuito de avaliar a associaÃÃo dos alelos do sistema HLA de classe II com caracterÃsticas clÃnicas e parÃmetros hematolÃgicos de pacientes com AF. Foram realizadas genotipagens para os loci DRB1 e DQB1 de 62 indivÃduos com diagnÃstico de AF, e de 86 indivÃduos saudÃveis (HbA2) usados como controle. As frequÃncias alÃlicas (Fa) foram obtidas pela contagem direta, e calculadas pela fÃrmula Fa = a/2n. No grupo com AF os cinco alelos HLA-DRB1 mais frequentes foram DRB1*04 (16,9%), DRB1*01 (12,9%), DRB1*08 (12,1%), DRB1*07 e DRB1*11 (ambos com 11,3%), os quais representam 64,5% da variabilidade total das 13 especificidades analisadas. Os trÃs alelos HLA-DQB1 mais frequentes foram DQB1*03 (45,2%), DQB1*05 (18,5%) e DQB1*06 (16,9%), correspondendo a 80,6% da variabilidade total dos 5 alelos analisados. Para o grupo controle os cinco alelos HLA-DRB1 mais frequentes foram DRB1*04 (16,3%), DRB1*13 (15,1%), DRB1*08 e DRB1*15 (ambos com 11,6%) e DRB1*07 (8,1%), os quais representam 62,7% da variabilidade total dos alelos avaliados para esse grupo. Quanto ao HLA-DQB1, os trÃs alelos mais frequentes foram o DQB1*03 (32,0%), DQB1*06 (22,7) e DQB1*05 (19,2%), correspondendo a 73,9% da variabilidade total dos alelos avaliados nesse grupo.Com relaÃÃo ao acidente vascular cerebral (AVC) os alelos DRB1*15 e DQB1*06 (p = 0,0033 e p = 0,0077, respectivamente) apresentaram uma frequÃncia elevada nos pacientes que manifestaram AVC. Para Ã sÃndrome torÃcica aguda (STA), os alelos DRB1*01 (p = 0,0398) e DQB1*06 (p = 0,0057) foram os mais frequentes no grupo com STA, enquanto que os alelos DRB1*01 (p =0,03980) e DQB1*05 (p = 0,0446) foram mais frequentes no grupo de pacientes que sem STA. NÃo foram encontradas associaÃÃes significativas com as dolorsas crises de vaso-oclusÃo. A hemoglobina total e o hematÃcrito (p = 0,045 e 0,0036, respectivamente) e a hemoglobina fetal (HbF)(p = 0,024), foram os Ãnicos parÃmetros hematolÃgico que tiveram associaÃÃo significativa, sendo o locus DQB1 responsÃvel por essa associaÃÃo. Em relaÃÃo Ã HbF, os alelos DQ02 e DQ06, foram associados a nÃveis mais baixos e mais altos, respectivamente, dessa fraÃÃo de hemoglobina nos pacientes estudados (p = 0,015). Nossos resultados fornecem a primeira evidÃncia de que os genes do sistema HLA estÃo envolvidos na modificaÃÃo do curso clÃnico e do surgimento de complicaÃÃes em indivÃduos com anemia falciforme no Brasil.

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Chang, Yea-wen. "Application of molecular genetic techniques to the study of major histocompatibility complex class II allelic associations with insulin-dependent diabetes mellitus in Chinese /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B18539919.

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Davis, Richard Elliot. "Neutrophil responses to infection with leishmania parasites: MHC class II-expression and parasite life-stage interactions." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2200.

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The vector-borne protozoan Leishmania spp. cause the spectrum of disease known as leishmaniasis in human and animal hosts. The most common manifestations of leishmaniasis are the chronic, ulcerative skin disease cutaneous leishmaniasis (CL), and the more serious visceral leishmaniasis (VL) in which parasites take up residence in internal organs, causing death if not treated. The role of neutrophils (PMNs) in the immune response to CL and VL is unclear. It is s generally thought that PMNs are only a short-lived effector cell, and have been disregarded as playing a role in chronic Leishmania spp. infection. As both CL and VL are diseases characterized by increased inflammatory immune mediators, we hypothesized that PMNs from human or animal models of chronic leishmaniasis would display different properties from PMNs from healthy controls. We found in a subset of CL and VL patients circulating PMNs expressing HLA-DR, the human form of MHC class II, a molecule thought to be restricted primarily to professional antigen cells. When we examined PMNs recruited to CL skin lesions in human patients, or similar lesions in experimental murine model of CL, we found significantly increased MHC class II+ PMNs. Circulating HLA-DR+ PMNs also expressed the co-stimulatory molecules CD80, CD86 and CD40. While this suggested an antigen-presenting cell-like phenotype by these HLA-DR+ PMNs, compared to conventional HLA-DR- PMNs, HLA-DR+ PMNs showed not only a neutrophil-like appearance and function, but in fact increased activation, degranulation, intracellular MPO and phagocytosis of parasites and zymosan particles. Incubation of healthy control whole blood with inflammatory cytokines resulted in increased HLA-DR+ PMNs and the presence of hladrb1 mRNA, suggesting a connection between neutrophil “priming” and upregulation of HLA-DR. In addition to HLA-DR+ PMNs in CL patients, we also identified the presence of so-called “low-density” neutrophils (LD-PMNs). These neutrophils, which are enriched in low-density fractions following centrifugation of blood over a density gradient, are reported in numerous disease states, including cancer, HIV, and systemic lupus erythematosus. In some disease states, LD-PMN are reported to be immunosuppressive toward T cell activation and proliferation. However, LD-PMNs from leishmaniasis patients showed no evidence of immunosuppression. Additionally, we found that LD-PMNs show significantly increased surface expression of MHC class II, suggesting a heretofore unappreciated connection between these atypical neutrophil phenotypes. We also investigated the in vitro interactions with different Leishmania infantum life-stages, both those that cause acute infection (promastigotes) and amastigotes, which are found during chronic stages of the disease. We found that PMNs are readily infected by all L. infantum life-stages, but that amastigotes may have different methods of interacting with PMN surface receptors and are better equipped to avoid PMN anti-microbial responses. These data suggest that circulating PMNs in chronic leishmaniasis may have unique phenotypes and interact differently with the Leishmania spp. life-cycle present during chronic infection. Further investigation of the role of PMNs and atypical PMN phenotypes in chronic disease may help identify new immunomodulatory roles for this cell type.

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Andersson, Svärd Agnes. "Peripheral blood cell HLA class II gene expression in children at genetic risk for type 1 diabetes and coeliac disease." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-267950.

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Melo, Luciane Moreno Storti de [UNESP]. "Avaliação da resposta de anticorpos contra antígenos de Plasmodium vivax relacionada a fatores genéticos do parasito e do hospedeiro humano." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/102752.

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O presente estudo avaliou a resposta de anticorpos contra diferentes antígenos de merozoíto e esporozoíto de Plasmodium vivax, relacionando com as variantes da porção repetitiva do domínio central do gene da Proteína Circunsporozoítica (CSP) do parasito (VK210, VK247 e P. vivax-like) e com os polimorfismos do HLA-DRB1 no hospedeiro humano. A resposta de anticorpos foi avaliada para peptídeos das regiões conservadas e centrais variáveis da CSP, da porção N-terminal da Proteína de Superfície do Merozoíto 1-MSP1 (Pv200L), e recombinante do Antígeno 1 de Membrana Apical (AMA-1) e a Proteína de ligação ao Duffy (DBP) por ELISA, em amostras de plasma de pacientes naturalmente infectados com P. vivax. Inicialmente nós avaliamos a distribuição destas variantes da CSP em cinco diferentes áreas da Amazônia a fim de entender sua atual dinâmica de transmissão. A variante VK210 continua sendo a mais prevalente em todas as áreas estudadas. No entanto, pela primeira vez documentamos a presença das variantes VK247 e P. vivax-like como infecções simples na Amazônia brasileira evidenciando um novo perfil distribuição destas, o que possa sugerir um processo de adaptação das mesmas. Quando comparamos a resposta de anticorpos e a infecção pelas variantes de P. vivax, não foram observadas associações significativas entre a presença de determinada variante da CSP e a freqüência de resposta de anticorpos contra os três peptídeos do merozoíto analisados, MSP1 (Pv200L), AMA-1 e DBP e nem contra as frações conservadas da CSP no esporozíto, N-terminal [N] e C-terminal [C]. A falta de associações significativas entre resposta sorológica contra esses peptídeos fornece informações promissoras quanto à utilização destes antígenos para o desenvolvimento de uma vacina contra malária. Todavia, a variação na porção central da CSP deve ser considerada...
The present study evaluated the antibody response against merozoite and sporozoite antigens of Plasmodium vivax and its relationship with the variants of the repetitive central region of the gene for Circunsporozoite protein (CSP) in parasite (VK210, VK247 and P. vivax-like) and, with the HLA-DRB1 polymorphisms in human host. The antibody response to synthetic peptides of the CSP conserved and variable regions and of the N-terminal portion of Merozoite surface protein - MSP1 (Pv200L), and, to recombinants peptides of the Apical Membrane Antige 1 (AMA-1) and of the Duffy Binding Protein (DBP) was evaluable by ELISA in plasma samples of malaria patients naturally infected with P. vivax. Firstly, we evaluated the CSP variants distribution among five different areas from Brazilian Amazon, in order to understand their current dynamic of transmissions. VK210 variant remains the most prevalent in all study areas. However, it is the first detection of VK247 e P. vivax-like variants as simple infection in the Brazilian Amazon, showing a new distribution profile, which may suggest an adaptation process of them. When comparing the antibody response and infection by variants of P. vivax, there were no significant associations between the presence of particular CSP variant and the frequency of antibody response against all three merozoite peptides analyzed, MSP1 (Pv200L), AMA-1, DBP and against the CSP conserved fractions in the sporozoite, N-terminal and C-terminal. The lack of significant associations among immune response against these peptides provides promising information regarding the use of these antigens for malaria vaccine development. On the other hand, the central variability of CSP should be considered to employment of this region as an immunogen, since the antibody response appears to be variant-specific. In order to evaluate the polymorphisms... (Complete abstract click electronic access below)

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Jackson, Andrew M. Naziruddin Bashoo. "Analysis of inflammatory changes in human pancreatic islet cells." Waco, Tex. : Baylor University, 2009. http://hdl.handle.net/2104/5344.

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42

Chang, Yea-wen, and 張雅雯. "Application of molecular genetic techniques to the study of major histocompatibility complex class II allelic associations with insulin-dependent diabetes mellitus in Chinese." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31213960.

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43

Melo, Luciane Moreno Storti de. "Avaliação da resposta de anticorpos contra antígenos de Plasmodium vivax relacionada a fatores genéticos do parasito e do hospedeiro humano /." São José do Rio Preto : [s.n.], 2011. http://hdl.handle.net/11449/102752.

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Orientador: Ricardo Luiz Dantas Machado
Banca: Cláudio Tadeu Daniel Ribeiro
Banca: Érika Martins Braga
Banca: Claudia Regina Bonini Domingos
Banca: Érika Cristina Pavarino Bertelli
Resumo: O presente estudo avaliou a resposta de anticorpos contra diferentes antígenos de merozoíto e esporozoíto de Plasmodium vivax, relacionando com as variantes da porção repetitiva do domínio central do gene da Proteína Circunsporozoítica (CSP) do parasito (VK210, VK247 e P. vivax-like) e com os polimorfismos do HLA-DRB1 no hospedeiro humano. A resposta de anticorpos foi avaliada para peptídeos das regiões conservadas e centrais variáveis da CSP, da porção N-terminal da Proteína de Superfície do Merozoíto 1-MSP1 (Pv200L), e recombinante do Antígeno 1 de Membrana Apical (AMA-1) e a Proteína de ligação ao Duffy (DBP) por ELISA, em amostras de plasma de pacientes naturalmente infectados com P. vivax. Inicialmente nós avaliamos a distribuição destas variantes da CSP em cinco diferentes áreas da Amazônia a fim de entender sua atual dinâmica de transmissão. A variante VK210 continua sendo a mais prevalente em todas as áreas estudadas. No entanto, pela primeira vez documentamos a presença das variantes VK247 e P. vivax-like como infecções simples na Amazônia brasileira evidenciando um novo perfil distribuição destas, o que possa sugerir um processo de adaptação das mesmas. Quando comparamos a resposta de anticorpos e a infecção pelas variantes de P. vivax, não foram observadas associações significativas entre a presença de determinada variante da CSP e a freqüência de resposta de anticorpos contra os três peptídeos do merozoíto analisados, MSP1 (Pv200L), AMA-1 e DBP e nem contra as frações conservadas da CSP no esporozíto, N-terminal [N] e C-terminal [C]. A falta de associações significativas entre resposta sorológica contra esses peptídeos fornece informações promissoras quanto à utilização destes antígenos para o desenvolvimento de uma vacina contra malária. Todavia, a variação na porção central da CSP deve ser considerada... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The present study evaluated the antibody response against merozoite and sporozoite antigens of Plasmodium vivax and its relationship with the variants of the repetitive central region of the gene for Circunsporozoite protein (CSP) in parasite (VK210, VK247 and P. vivax-like) and, with the HLA-DRB1 polymorphisms in human host. The antibody response to synthetic peptides of the CSP conserved and variable regions and of the N-terminal portion of Merozoite surface protein - MSP1 (Pv200L), and, to recombinants peptides of the Apical Membrane Antige 1 (AMA-1) and of the Duffy Binding Protein (DBP) was evaluable by ELISA in plasma samples of malaria patients naturally infected with P. vivax. Firstly, we evaluated the CSP variants distribution among five different areas from Brazilian Amazon, in order to understand their current dynamic of transmissions. VK210 variant remains the most prevalent in all study areas. However, it is the first detection of VK247 e P. vivax-like variants as simple infection in the Brazilian Amazon, showing a new distribution profile, which may suggest an adaptation process of them. When comparing the antibody response and infection by variants of P. vivax, there were no significant associations between the presence of particular CSP variant and the frequency of antibody response against all three merozoite peptides analyzed, MSP1 (Pv200L), AMA-1, DBP and against the CSP conserved fractions in the sporozoite, N-terminal and C-terminal. The lack of significant associations among immune response against these peptides provides promising information regarding the use of these antigens for malaria vaccine development. On the other hand, the central variability of CSP should be considered to employment of this region as an immunogen, since the antibody response appears to be variant-specific. In order to evaluate the polymorphisms... (Complete abstract click electronic access below)
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Yin, Liusong. "Studies of HLA-DM in Antigen Presentation and CD4+ T Cell Epitope Selection: A Dissertation." eScholarship@UMMS, 2014. http://escholarship.umassmed.edu/gsbs_diss/700.

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Antigen presented to CD4+ T cells by major histocompatibility complex class II molecules (MHCII) plays a key role in adaptive immunity. Antigen presentation is initiated by the proteolytic cleavage of pathogenic or self proteins and loading of resultant peptides to MHCII. The loading and exchange of peptides to MHCII is catalyzed by a nonclassical MHCII molecule, HLA-DM (DM). It is well established that DM promotes peptide exchange in vitro and in vivo. However, the mechanism of DM-catalyzed peptide association and dissociation, and how this would affect epitope selection in human responses to infectious disease remain unclear. The work presented in this thesis was directed towards the understanding of mechanism of DM-mediated peptide exchange and its role in epitope selection. In Chapter II, I measured the binding affinity, intrinsic dissociation half-life and DM-mediated dissociation half-life for a large set of peptides derived from vaccinia virus and compared these properties to the peptide-specific CD4+ T cell responses. These data indicated that DM shapes the peptide repertoire during epitope selection by favoring the presentation of peptides with greater DM-mediated kinetic stability, and DM-susceptibility is a strong and independent factor governing peptide immunogenicity. In Chapter III, I computationally simulated peptide binding competition reactions and found that DM influences the IC50 (50% inhibition concentration) of peptides based on their susceptibility to DM, which was confirmed by experimental data. Therefore, I developed a novel fluorescence polarization-based method to measure DM-susceptibility, reported as a IC50 (change in IC50 in the absence and presence of DM). Traditional assays to measure DM-susceptibility based on differential peptide dissociation rates are cumbersome because each test peptide has to be individually labeled and multiple time point samples have to be collected. However, in this method developed here only single probe peptide has to be labeled and only single reading have to be done, which allows for fast and high throughput measure of DM-susceptibility for a large set of peptides. In Chapter IV, we generated a series of peptide and MHCII mutants, and investigated their interactions with DM. We found that peptides with non-optimal P1 pocket residues exhibit low MHCII affinity, low kinetic stability and high DM-susceptibility. These changes were accompanied with conformational alterations detected by surface plasmon resonance, gel filtration, dynamic light scattering, small-angle X-ray light scattering, antibody-binding, and nuclear magnetic resonance assays. Surprisingly, all these kinetic and conformational changes could be reversed by reconstitution with a more optimal P9 pocket residue. Taken together, our data demonstrated that conformation of MHCII-peptide complex constrained by interactions throughout the peptide binding groove is a key determinant of DM-susceptibility. B cells recognizing cognate antigen on the virion can internalize and process the whole virion for antigen presentation to CD4+ T cells specific for an epitope from any of the virion proteins. In turn, the epitope-specific CD4+ T cells provide intermolecular (also known as noncognate or heterotypic) help to B cells to generate antibody responses against any protein from the whole virion. This viral intermolecular help model in which CD4+ T cells provide help to B cells with different protein specificities was established in small size influenza virus, hepatitis B virus and viral particle systems. For large and complex pathogens such as vaccinia virus and bacteria, the CD4+ T cell-B cell interaction model may be complicated because B cells might not be able to internalize the large whole pathogen. Recently, a study in mice observed that CD4+ T cell help is preferentially provided to B cells with the same protein specificity to generate antibody responses against vaccinia virus. However, for larger pathogens such as vaccinia virus and bacteria the CD4+ T cell-B cell interaction model has yet to be tested in humans. In Chapter V, I measured in 90 recently vaccinated and 7 long-term vaccinia-immunized human donors the CD4+ T cell responses and antibody responses against four vaccinia viral proteins (A27L, A33R, B5R and L1R) known to be strongly targeted by cellular and humoral responses. We found that there is no direct linkage between antibody and CD4+ T cell responses against each protein. However, the presence of immune responses against these four proteins is linked together within donors. Taken together, our data indicated that individual viral proteins are not the primary recognition unit and CD4+ T cells provide intermolecular help to B cells to generate robust antibody responses against large and complicated vaccinia virus in humans.

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45

Scott, Carol Elizabeth DeWeese. "Molecular modeling and experimental characterization of HLA-DQ proteins and protein/peptide complexes : correlation with insulin-dependent diabetes mellitus (IDDM) /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/8089.

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46

Odeberg, Jenny. "Human cytomegalovirus immune evasion strategies /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-126-8.

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47

Garban, Frédéric. "Les molécules HLA de classe II dans les lymphocytes B de sang de cordon : présentation de l'antigène - transmission de signaux." Paris 7, 1997. http://www.theses.fr/1997PA077218.

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Les lymphocytes b de sang de cordon sont des cellules matures mais protegees des rencontresantigeniques exogenes. Les molecules hla de classe ii sont le support de la presentation antigenique et de la transmission de signaux intracellulaires d'activation ou de mort cellulaire programmee. Les cellules b de sang de cordon presentent de grandes quantites de molecules hla de classe ii vides mais la capacite d'allostimulation est preservee. Ces molecules hla de classe ii se presentent comme chez l'adulte sous forme de dimeres de dimeres, mais a la surface des lymphocytes b adultes la quantite de molecules vides est faible. En revanche, plusieurs milliers de sites vides existent a la surface des monocytes. L'etude de la signalisation via les molecules hla-dr montre un deficit de la mobilisation du calcium intracellulairedans les lymphocytes b de cordon avec deficit de l'agregation homotypique et de l'induction de l'apoptose. Ce deficit de l'apoptose est relie a l'absence de flux calcique. Des similitudes existent entre la signalisation via hla dr des cellules b de cordon et de certaines hemopathies lymphoides bchroniques (leucemie lymphoide chronique) et lymphome du manteau) avec une difference importante en ce qui concerne l'activation de la proteine kinase c. Ces donnees permettent d'approfondir nos connaissances sur les premiers stades de l'ontogenie des lymphocytes b apres la sortie de la moelle en apportant des elements sur la fonction des molecules hla de classe ii au cours de l'ontogenie.

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48

Azam, Aurélien. "Etude de la réponse des lymphocytes T spécifiques de l’hormone humaine H2-relaxine et de modifications non-naturelles : perspectives pour la réduction de l’immunogénicité des protéines et peptides thérapeutiques." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS140/document.

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Ce projet a accompagné le développement pré-clinique de l'hormone humaine Relaxine-2 (Rln2) ayant induit des anticorps durant des essais cliniques, il est axée autour de 2 problématiques : (1) comprendre son immunogénicité, (2) étudier l’impact de modifications chimiques sur l’immunogénicité afin d'augmenter sa stabilité.Compte tenu du rôle des lymphocytes T CD4 dans les réponses immunitaires, la fréquence de cellules T spécifiques de la Rln2 dans un large panel de donneurs sains a été estimée et a permis d’expliquer le développement d’anticorps anti-Rln2. La cartographie des épitopes T a ensuite identifié les zones portant son immunogénicité. Puis, 6 modifications chimiques (acide aminé D, acide aminé isobutyrique, peptoïde, N-méthylation, C-méthylation et réduction de la liaison peptidique) utilisées pour augmenter la demi-vie ont été introduites à la plupart des positions d’un peptide hautement immunogène. La reconnaissance par des cellules T, la liaison aux molécules de présentation et la capacité à induire des lymphocytes T CD4 ont été étudiées pour les peptides analogues modifiés. La plupart des modifications se sont révélées être très efficaces pour minimiser les propriétés immunogéniques.Ce projet de thèse se situe donc à la croisée des chemins entre l’acquisition de connaissances nouvelles en immunologie et leur application dans des processus de conception et de gestion des risques de peptides thérapeutiques
This project has accompanied the pre-clinical development of the human hormone Relaxin-2 (Rln2) that induced antibodies during clinical trials, it focuses on two issues: (1) to understand its immunogenicity, (2) to study the impact of unnatural modifications on immunogenicity to increase its stability.Given the role of CD4 T-cells in immune responses, the frequency of Rln2-specific T-cells in a large panel of healthy donors was estimated, and explained the development of anti-Rln2 antibodies. The T epitope mapping then identified the areas responsible for its immunogenicity. Then, 6 unnatural modifications (D amino acid, amino isobutyric acid, peptoid, N-methylation, C-methylation & reduced peptide bond) used to increase the half-life were introduced at most positions of a highly immunogenic peptide. T-cell recognition, binding to HLA molecules and the ability to induce CD4 T-cells were studied for modified analog peptides. Most of the modifications were very effective in minimizing immunogenic properties.This thesis project is at the crossroads between the acquisition of new knowledge in immunology and its application in the process of design & risk management of therapeutic peptides

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Moberg, Martin. "Human Papillomavirus Load and Cervical Carcinoma." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4256.

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Néel, Dominique. "Caracterisation des oligosaccharides n-lies d'antigenes hla-dr et de leurs cellules vectrices : contribution a l'etude des facteurs influencant la n-glycosylation." Paris 7, 1987. http://www.theses.fr/1987PA077138.

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Dissertations / Theses on the topic 'HLA class II geners'

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