Rozprawy doktorskie na temat „Killer immunoglobulin like receptors (KIR)”
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Yindom, Louis Marie. "Human Leukocyte Antigen (HLA) and Killer Immunoglobulin-like Receptors (KIR) in HIV-2 Infection". Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520671.
Pełny tekst źródłaBraun, Kali. "Association of killer immunoglobulin-like receptor (KIR) genes with tuberculosis disease in two Canadian cohorts". PLoS ONE, 2013. http://hdl.handle.net/1993/22042.
Pełny tekst źródłaSepulveda, Christian Alberto Garcia. "Killer cell Immunoglobulin-like Receptor (KIR) polymorphism : functional implications and clinical relevance". Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444690/.
Pełny tekst źródłaHalfpenny, Iris A. "An investigation into the genetics of the killer immunoglobulin-like receptor (KIR) gene family". Thesis, University of Ulster, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494359.
Pełny tekst źródłaFoley, Bree Amanda. "The immunogenetics of natural killer cell alloreactivity". University of Western Australia. School of Pathology and Laboratory Medicine, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0242.
Pełny tekst źródłaSalim, Patrícia Hartstein. "Estudo do polimorfismo dos genes KIR na esclerose sistêmica". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2009. http://hdl.handle.net/10183/15457.
Pełny tekst źródłaNatural killer (NK) cells have an important role in the early responses to viral infections. They kill diverse target cells with decreased or absent expression of major histocompatibility complex (MHC) class I molecules through the Killer Cell Immunoglobulin-Like Receptors (KIR). Many studies have reported association of KIR genes with autoimmune diseases. The objective of this study is to investigate possible associations of KIR polymorphisms with systemic sclerosis (SSc), including the limited (lSSc) and diffuse (dSSc) forms of the disease. The frequency of inhibitory KIR2DL2 was significantly decreased among patients with SSc compared with healthy controls (28.7% versus 65.2; P<0.001, odds ratio [OR] 0.21, 95% confidence interval [95% CI] 0.11–0.38). When activatory and inhibitory KIR genes were analyzed in combination, the concomitant presence of KIR2DS2 and absence of KIR2DL2 (KI2DS2+/KIR2DL2-) phenotype was more frequent in SSc patients than in the control group (26.08% versus 1.75%; P<0.001, OR=19.94, 95%CI [4.78–175.10]). On the other hand, the presence of both KIR2DS2 and KIR2DL2 was more frequent in the control group (26.96% versus 57.39%; P=0.000005, OR=0.27, 95%CI [0.15–0.49]). No significant difference in KIR genes polymorphisms was found between lSSc and dSSc disease subsets. The combination of KIR2DS2+/KIR2DL2– may be a risk factor for development of SSc while the higher frequency of the inhibitory KIR2DL2 gene in the control group suggest to a protective effect. These results indicate a potential role of KIR genes in the SSc pathogenesis.
Ishida, Yoshihiro. "Killer immunoglobulin-like receptor genotype did not correlate with response to anti-PD-1 antibody treatment in a Japanese cohort". Kyoto University, 2020. http://hdl.handle.net/2433/253207.
Pełny tekst źródłaSilva, Pamela Portela da. "Análise de polimorfismos dos genes KIR e HLA classe I em pacientes com câncer colorretal". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/148088.
Pełny tekst źródłaColorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 healthy controls by PCR-SSO and PCR-SSP. When both groups were compared, no significant differences were found for HLA ligands and KIR genes after Bonferroni correction. However, the Bx group genotypes (heterozygous and homozygous for the haplotype B) were more frequent in controls, when compared with patients. These findings suggest that individuals with Bx genotypes could have some protection to colorectal cancer. These findings suggest that higher levels of activating KIR signals appear as protective to colorectal cancer.
Silva, Pamela Portela da. "Estudo de polimorfismos dos genes KIR e HLA em pacientes com câncer de próstata". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/35890.
Pełny tekst źródłaProstate cancer is the second most common cancer among men, since both incidence and mortality exponentially increases in men over fifty years of age. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA alleles in patients with prostate cancer and healthy controls. Two hundred prostate cancer patients and 185 healthy controls were typed for HLA class I and KIR genes by PCR-SSP. When both groups were compared, no significant differences were found for HLA-C group 1 and group 2, HLA-Bw4, HLA-A3 and A11. No difference was seen either in KIR frequency between patients with prostate cancer and controls. In conclusion, our data suggests no potential role for the KIR gene system in prostate cancer.
Ichise, Hiroshi. "NK cell alloreactivity against KIR-ligand-mismatched HLA-haploidentical tissue derived from HLA haplotype-homozygous iPSCs". Kyoto University, 2017. http://hdl.handle.net/2433/228232.
Pełny tekst źródłaJobim, Maria Regina Sampaio Leite. "Estudo do polimorfismo dos genes KIR e HLA em pacientes com câncer de mama e grupo controle". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/97026.
Pełny tekst źródłaWe investigated the frequency of various KIR (Killer Immunoglobulin-like Receptors) and HLA C1 and C2 gene polymorphisms in a group of patients with breast cancer and healthy controls. Natural Killer (NK) cells are lymphocytes that differ from T and B cells and are part of the innate immune system, recognizing class I Human Leukocyte Antigens (HLA) molecules on target cells (virus-infected as well as cancer cells), through specific cell surface receptors. KIR comprises the main class of NK receptors, being encoded by genes located in chromosome 19q13.4. They possess both suppressor and activating functional groups. Fifteen KIR genes and class I HLA alleles obtained from 230 Caucasians patients, as well as 278 controls were studied, using PCR techniques with specific primers (PCR-SSO and PCR-SSP). Our results showed a higher frequency of suppressor genotype 2DL2 (P<0,001) in patients with breast cancer as compared to controls. No significant difference between HLA-C2 and HLA-BW4 alleles were observed between the study groups. Notably, a higher frequency of HLA-C1 gene was noted in patients with breast cancer. Our results suggest a potential association between KIR genes, HLA class I and breast cancer, deserving further investigation.
Kruse, Philip Hermann Verfasser], Lutz [Akademischer Betreuer] Walter, Jürgen [Akademischer Betreuer] [Wienands i Wolfgang [Akademischer Betreuer] Engel. "Genetic and functional characterisation of killer cell immunoglobulin like receptors (KIR) of rhesus macaques (Macaca mulatta) / Philip Hermann Kruse. Gutachter: Lutz Walter ; Jürgen Wienands ; Wolfgang Engel. Betreuer: Lutz Walter". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2011. http://d-nb.info/1042640025/34.
Pełny tekst źródłaMartin, Hilmar. "Evaluation von KIR-Liganden Inkompatibilität bei unverwandten Knochenmark-/ Stammzelltransplantationen". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2005. http://nbn-resolving.de/urn:nbn:de:swb:14-1124306558415-94790.
Pełny tekst źródłaIn der Therapie von Leukämien ist die Knochenmark- bzw. Stammzelltransplantation eine tragende Säule. Für den Transplantationserfolg ist eine Übereinstimmung der Haupthistokompatibilitätsantige (HLA-Antigene der Klassen I und II) zwischen Spender und Empfänger von zentraler Bedeutung. Diese Notwendigkeit ergibt sich aus der sogenannten MHC-Restriktion in der T-Zellrezeptorerkennung. Ob auch NK-Zellrezeptoren und deren Liganden in der Spenderauswahl berücksichtigt werden sollten, ist bisher unzureichend untersucht. Insbesondere trifft das für die KIR-Rezeptoren zu, die wie die T-Zellrezeptoren ebenfalls HLA-Antigene als Liganden besitzen. Velardi et al. haben 2002 erstmalig gezeigt, daß in der Therapie myeloischer Leukämien die Transplantation von Blutstammzellen verwandter Spender mit KIR-Liganden-Inkompatibilität von klinischem Vorteil ist. Ob KIR-Liganden-Inkompatibilität auch bei Knochenmark-/ Stammzelltransplantationen Unverwandter Bedeutung erlangen könnte, war zu Studienbeginn offen und blieb auch infolge diskrepanter Untersuchungsergebnisse von verschiedenen Arbeitsgruppen im Verlauf der Studie widersprüchlich. Im Rahmen dieser Arbeit wurde diese Fragestellung, die auch Teil einer internationalen Studie war, an 185 Spender-Empfänger-Paaren retrospektiv untersucht. Dabei wurde bei den Paaren einerseits die KIR-Liganden-Kompatibilität auf der Grundlage der HLA-C-Supertypen erschlossen (nach Velardi et al.). Andererseits konnte sie im internationalen Studienprogramm direkt aus dem KIR-Genotyp des Spenders und dem HLA-C-Supertyp des Empfängers ermittelt werden. Die Untersuchungen ergaben folgende Resultate: bei Vorliegen von KIR-Liganden-Inkompatibilität hat die Verwendung von ATG als Bestandteil der GvHD-Prophylaxe keinen Einfluß auf das klinische Ergebnis. Die Vermutungen von Giebel et al. wurden damit nicht gestützt. Die Bestimmung des KIR-Liganden-Status mit Hilfe der Rückschlußmethode allein aus dem HLA-Typ ist unzuverlässig. Für eine exakte Differenzierung ist die gleichzeitige KIR-Genotypisierung erforderlich. KIR-Liganden-Inkompatibilität ist bei unverwandten Knochenmark-/ Stammzelltransplantationen nicht von klinischem Vorteil. Auch ein gezieltes Aussuchen HLA-C-inkompatibler Spender auf der Grundlage einer KIR-Genotypisierung stellt derzeit keine therapeutische Option dar
Abalos, Andrew T. "KILLER-CELL IMMUNOGLOBULIN-LIKE RECEPTORS AND HPV PREVALENCE AND INCIDENCE". Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/145440.
Pełny tekst źródłaTwigger, Katie. "The role of killer immunoglobulin-like receptors in HTLV-1 infection". Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/25539.
Pełny tekst źródłaSpeidel, Frieder. "Untersuchungen zur Expression von "Killer-immunoglobulin-like-receptors" und zytotoxischer Aktivität von cytokinstimulierten NK-Zellen /". Tübingen, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253677.
Pełny tekst źródłaMoesta, Achim Klaus. "Functional specificities of killer cell immunoglobulin-like receptors for MHC-C in humans and chimpanzees /". May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Pełny tekst źródłaThielens, Ariane. "Etudes pré-clinique et clinique de l'anticorps immunomodulateur Lirilumab visant à augmenter la réponse anti-tumorale des cellules NK". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4105.
Pełny tekst źródłaNK cell anti-tumoral activity is regulated by inhibitory and activating receptors interacting with target cell ligands. Innate Pharma has developed anti-KIR Abs (IPH2101 and lirilumab), directed against inhibitory NK cell receptors interacting with HLA molecules, in order to increase NK cell activity against autologous tumor cells.We have set up a preclinical model to assess anti-KIR anti-tumoral efficacy in transgenic mice expressing a KIR receptor. With this model, we have also shown the therapeutic benefit of combining lirilumab with rituximab, a therapeutic Ab mediating ADCC.These results support the rationale of combining anti-KIR Ab with Ab mediating ADCC as a therapeutic strategy for hematological malignancies
Older, Aguilar Anastazia Magdalena. "Comparison of genomic structure and MHC specificities of killer cell immunoglobulin-like receptors in humans and orangutans /". May be available electronically:, 2009. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Pełny tekst źródłaSáez, Borderias Andrea. "Regulation of natural killer and cd4+T cell function by NKG2 C-type lectin-like receptors". Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7133.
Pełny tekst źródłaAquesta tesi es centra en l'estudi dels receptors lectina de tipus C NKG2 en cèl·lules Natural Killer i T CD4+. Demostrem que les cèl·lules T CD4+ específiques pel Cytomegalovirus Humà poden expressar diferents receptors NK, i que el receptor lectina tipus C NKG2D s'expressa en cèl·lules citotòxiques i de memòria, potenciant la proliferació i secreció de citocines depenent del TCR. La segona part d'aquesta tesi es centra en l'estudi de l'expressió dels receptors CD94/NKG2 en cèl·lules NK. Mostrem com l'expressió de CD94/NKG2A s'indueix en cèl·lules CD94/NKG2C+ estimulades amb IL-12 o cultivades amb cèl·lules dendrítiques infectades pel Cytomegalovirus Humà, i que l'expressió de CD94/NKG2A inhibeix la resposta de clons NK CD94/NKG2C+ envers dianes HLA-E+, constituint un possible mecanisme de feedback negatiu per controlar l'activació cel·lular. En resum, els nostres resultats demostren que l'expressió dels receptors lectina tipus C NKG2 pot ser modificada durant les infeccions víriques consitutint un possible mecanisme per regular la resposta tant de cèl·lules NK com T CD4+.
Hermes, Meike [Verfasser], Lutz [Akademischer Betreuer] Walter i Torben [Akademischer Betreuer] Lübke. "Characterisation of killer immunoglobulin-like receptors in rhesus macaques (Macaca mulatta) / Meike Hermes. Gutachter: Lutz Walter ; Torben Lübke. Betreuer: Lutz Walter". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2012. http://d-nb.info/1042345627/34.
Pełny tekst źródłaSuck, Garnet, Yeh Ching Linn i Torsten Tonn. "Natural Killer Cells for Therapy of Leukemia". Karger, 2016. https://tud.qucosa.de/id/qucosa%3A71644.
Pełny tekst źródłaPesce, John Thomas. "Early events leading to the host protective Th2 immune response to an intestinal nematode parasite /". Download the dissertation in PDF, 2005. http://www.lrc.usuhs.mil/dissertations/pdf/Pesce2005.pdf.
Pełny tekst źródłaHermes, Meike. "Characterisation of killer immunoglobulin-like receptors in rhesus macaques (Macaca mulatta)". Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-F0C1-A.
Pełny tekst źródłaKruse, Philip Hermann. "Genetic and functional characterisation of killer cell immunoglobulin like receptors (KIR) of rhesus macaques (Macaca mulatta)". Doctoral thesis, 2010. http://hdl.handle.net/11858/00-1735-0000-0006-ADED-9.
Pełny tekst źródłaGentle, Nikki Lynne. "The role of killer immunoglobulin-like receptors (KIR) and specific human leukocyte antigen (HLA) class I molecules in control of HIV-1 infection". Thesis, 2015. http://hdl.handle.net/10539/18671.
Pełny tekst źródłaThe classical human leukocyte antigen (HLA) class I molecules are important regulators of both the adaptive and innate immune responses to viral infection. Genetic variability within these loci determines the nature of the interaction between both the T cell receptor (TCR) on CD8+ T cells and specific killer immunoglobulin-like receptors (KIR) on the surface of natural killer (NK cell). Both of these interactions have previously been demonstrated to be important in determining the course of HIV-1 disease outcome. We therefore examined patterns of genetic variability within both of these complex gene families in individuals from the Black South African population group, contrasting them with genetic variability observed within the corresponding loci in Caucasian South Africans and demonstrated associations between specific genetic variants within the HLA and KIR gene complexes and HIV-1 control in the Black South African population. Examination of genetic diversity within the KIR gene complex in the Black and Caucasian South African population groups revealed these two population groups differed significantly with respect to their KIR2DS1 and KIR3DS1 gene frequencies, as well as with respect to the full-length (KIR2DS4f) and truncated (KIR2DS4v) forms of KIR2DS4. Like KIR2DS1 and KIR3DS1, KIR2DS4v was most frequently observed in the Caucasian population group, while KIR2DS4f was more frequently observed within the Black population group. These differences could be attributed to the different frequency distributions of specific telomeric KIR haplotype motifs within these two population groups. These findings are of particular importance in the South African context, given the associations of KIR2DS4 and KIR3DS1 with both HIV-1 transmission and disease progression. An insertion-deletion (indel) polymorphism within the 3' untranslated region (UTR) of HLA-C has also been shown to be involved in the regulation of HLA-C expression. Individuals who carry a deletion at this position exhibit increased HLA-C expression, which associates with lower viral set point in HIV-1 infected individuals. This 263 indel (rs67384697) is reported to be in strong linkage disequilibrium (LD) with a single nucleotide polymorphism (SNP) 35 kilobases upstream of HLA-C (-35T/C; rs9264942) in Caucasian individuals, making this SNP a potential marker for both HLA-C expression and HIV-1 disease progression. We therefore examined genetic variation within the UTRs of the HLA-C alleles present in Black and Caucasian South Africans and identified two overlapping haplotypes encompassing the 263 indel and another indel at position 230 in both populations, which we propose may act in concert to regulate levels of HLA-C expression. Concomitant evaluation of variability at the -35 SNP revealed this polymorphism to be an inappropriate marker for either indel in these populations. Recently, individual polymorphic amino acids within the classical HLA class I loci, located predominantly within the peptide binding groove, have been shown to be strongly associated with HIV-1 control. We, therefore, examined patterns of genetic variability within and across the HLA class I loci in Black South African HIV-1 progressors and –controllers. Our findings confirmed those from other populations, demonstrating the importance of HLA-B residues 67, 70, 97 and 116 in determining disease outcome, while also identifying additional residues in HLA-A and -B that may potentially contribute to determining differential disease outcome in this population. Variability at these residues likely impacts the specificity of the peptide bound by the HLA molecule, resulting in differential regulation of both cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses. No significant associations were observed between HIV- 1 control and variability within either the HLA-C peptide binding groove or the 3’ UTR. Finally, we examined the role of genetic variability within the KIR gene complex in regulating HIV-1 control by examining patterns of genetic variability within this locus in Black South African HIV-1 progressors and –controllers. We found loss of control to be significantly associated with specific KIR haplotype motifs lacking KIR2DS4 and KIR3DL1, while maintenance of viral control was found to be associated with possession of KIR haplotypes containing the centromeric cB01 motif. Furthermore, elite controllers were more frequently found to be in possession of cB01 motifs containing KIR2DS5, rather than KIR2DS3. In light of the strong linkage disequilibrium observed across this region, KIR2DS3 and KIR2DS5 are thought act as markers for specific allelic variants of the inhibitory receptors KIR2DL1 and KIR2DL2, which are known to mediate differential inhibition of NK cell function. Collectively, these data represent the first comprehensive description of genetic variability within the KIR gene complex in Black South Africans and provide the valuable insights into the role of these receptors in mediating control of HIV-1 infection through interaction with their HLA class I -encoded ligands.
Albrecht, Christina. "Association of killer immunoglobulin-like receptor genes with viral loads in experimental SIV infection of rhesus macaques (Macaca mulatta)". Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-EF91-8.
Pełny tekst źródłaJesus, Kátia Ribeiro de. "Immunology and genetics in nonhuman primates: Study of KIR3DL02 interaction with MHC-class-I ligands of rhesus macaques". Master's thesis, 2018. http://hdl.handle.net/10316/82073.
Pełny tekst źródłaCélulas natural killer (NK) são linfócitos capazes de matar células alvo infectadas ou transformadas por vírus. A ativação da lise de células alvo pelas células NK é mediada pelos receptores presentes nestas células. Um grupo importante de receptores são os receptores tipo imunoglobulina das células killer (KIR), sabe-se que estes ligam a membros da família polimórfica de moléculas MHC-classe-I. O macaco rhesus foi considerado um modelo animal primata não-humano de grande importância para doenças infeciosas nos humanos. Durante infecção experimental com o vírus da imunodeficiência símia (SIV), foi estabelecida uma conexão entre a presença de certos KIR e alelos MHC-classe-I com maiores ou mais baixos níveis virais, e consequentemente com uma mais rápida ou mais lenta progressão da doença. Curiosamente, foi demonstrado que a expressão de KIR3DL02 está associada com níveis virais mais baixos em animais em ensaios experimentais de infecção. Contudo, as especificações da interação entre KIR3DL02 e ligandos de MHC-classe-I são desconhecidas. O objetivo do presente trabalho, foi, por um lado, estudar a interação entre KIR3DL02 e certos alelos de Mamu, através do uso de proteínas recombinantes de KIR-Fc multimerizadas para marcar células que expressam Mamu. Para além disto, de modo a expandir o espectro de futuros estudos de interação, novos alelos de Mamu foram amplificados de cDNA de macaco rhesus e clonados em vectores de expressão de mamíferos. O trabalho aqui descrito permitiu a otimização dos estudos de ligação com o uso de proteínas KIR-Fc de fusão e células K-562 transfectadas com Mamu AcGFP. Identificação de potenciais ligandos para KIR3DL02 assim como construção de novos vectores de expressão de Mamu foram conseguidos com sucesso. Contudo, é necessária a realização de mais estudos para averiguar os resultados aqui descritos e para estudar a interação entre KIR3DL02 e os novos alelos de Mamu amplificados, com especial interesse no alelo Mamu B*008 por estar associado a um efeito protetivo.
Natural killer (NK) cells are lymphocytes that are able to kill virus infected or transformed target cells. The activation of the NK cell mediated target cell lysis is achieved by the action of NK cell receptors. An important group of receptors are the killer cell Ig-like receptors (KIR), which are known to bind members of the polymorphic family of MHC-class-I molecules. The rhesus macaque has been considered of great importance as a nonhuman primate model of human infectious diseases. During experimental simian immunodeficiency virus (SIV) infection, a connection has been established between the presence of certain KIR and MHC-class-I alleles with higher or lower viral load, and consequently to faster or slower progression of the disease. Interestingly, the expression of KIR3DL02 transcripts was shown to be associated with low viral loads and elite controller animals. However, the specificity of interaction between KIR3DL02 and MHC-class-I ligands is unknown. The aim of the present work was, for one, study the interaction between KIR3DL02 and certain Mamu alleles using multimerized KIR-Fc recombinant proteins to stain Mamu expressing cells. Additionally, in order to widen the spectrum of future interaction studies, new Mamu alleles were amplified from cDNA of rhesus macaque and cloned into a mammalian expression vector. The present work allowed the optimization of binding assays using KIR-Fc fusion proteins with K-562 Mamu AcGFP transfected cells. Identification of potential KIR3DL02 ligands as well as production of new Mamu mammalian expression constructs was accomplished. However, further studies need to be conducted to verify results here described and to study interaction between KIR3DL02 and new Mamu alleles amplified. Herein, in special, the known protective Mamu B*008 allele.
Hardie, Rae-Anne Michelle. "Sequence-based genotyping of killer cell immunoglobulin-like receptors and their associations with HIV-1 resistance and disease progression". 2009. http://hdl.handle.net/1993/21431.
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