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Littérature scientifique sur le sujet « BCR repertoire »

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Publié le 25 mai 2024

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Articles de revues sur le sujet "BCR repertoire"

Harding, Taylor, Qidi Yang, Brittany Mineo, Jenna Malinauskas, Jason Perera, Karl Beutner, Denise Lau et Aly Khan. « 73 Characterization of tumor-infiltrating T-cell repertoire in human cancers ». Journal for ImmunoTherapy of Cancer 9, Suppl 2 (novembre 2021) : A81. http://dx.doi.org/10.1136/jitc-2021-sitc2021.073.

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BackgroundTCR and BCR repertoire profiling is a promising technique that can provide a clinically useful window into the complex interactions between tumor cells and infiltrating lymphocytes. Despite recent advances in repertoire sequencing methods, the characterization of tumor-infiltrating T-cell repertoires has been limited to small sample sizes due to technical and material constraints. In this study, we constructed a large multidimensional database of repertoire data covering a diverse landscape of HLA genotypes and tumor neoantigens from routine clinical sequencing. We present a descriptive summary of repertoire profiles derived from tens of thousands of tumor samples from over fifty different cancer cohorts and characterize the associations between T-cell repertoires and various clinical and molecular features.MethodsTo enrich immune receptor transcripts detected by the Tempus RNA-sequencing workflow, hybrid capture probes tiling TCR and BCR genes were used. Repertoire profiling reads were aligned, assembled, and annotated against IMGT reference sequences. Repertoires are profiled as a component of Tempus|xT RNA sequencing and are summarized here for >25 thousand tumor samples from over 50 different cancer cohorts.ResultsWe demonstrate that the use of TCR/BCR hybrid capture probes is an effective method for enriching immune receptor transcripts in RNA-sequencing data without interfering with downstream transcriptomic analysis. These repertoires were profiled as part of a larger, multimodal DNA/RNA-sequencing pipeline that quantifies a variety of tumor clinical and molecular features. We explored the correlation between high-level repertoire metrics like richness (the number of unique receptor clonotypes in a given repertoire) and clonality/evenness (Shannon entropy) against both gene expression-based metrics (i.e. immune cell infiltration estimates, etc.) and mutational patterns (mutational burden and neoantigen load). Finally, we observed that the repertoire clonality of B-cell and T-cell driven cancers frequently exhibits clear monoclonal dominance for the tumor cells’ lymphoid receptors.ConclusionsTCR/BCR repertoire profiling can be incorporated into high-volume clinical RNA sequencing to generate a diverse multimodal dataset for studying the tumor-immune microenvironment. By creating a large-scale database of TCR/BCR repertoire profiles from a variety of tissue, HLA genotypes, and mutational contexts, we can better resolve the molecular and clinical correlates of cancer with host adaptive immunity.

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Gupta, Neetu, Christina Labib, Veronique Giudicelli, Safa Aouinti, Marie-Paul Lefranc et Sofia Kossida. « Cytoskeletal control of the developing and mature B cell antigen receptor repertoire ». Journal of Immunology 204, n^o 1_Supplement (1 mai 2020) : 151.13. http://dx.doi.org/10.4049/jimmunol.204.supp.151.13.

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Abstract The existence of diverse B cell antigen receptor (BCR) specificities is essential for development of protective antibody responses against a wide variety of pathogens. In developing B cells, the BCR repertoire is crafted through sequential rearrangements of heavy and light chain genes, and involves both combinatorial and junctional diversification catalyzed by recombinases and nucleases. Mature B cells undergo further diversification in peripheral lymphoid organs through isotype switching and somatic hypermutations in response to foreign antigens; although these events are not known to alter BCR antigen specificity. Cytoskeletal proteins modulate BCR signal strength and thereby antibody responses, but it is not known if they play a role in the generation of BCR diversity. Using next generation sequencing, and iRepertoire, Inc and ImMunoGeneTics (IMGT) software platforms we examined BCR repertoires in developing and mature B cells that lack the expression of Ezrin, a prominent cytoskeletal regulator of BCR organization, signaling and activation. We show that Ezrin deficiency impacts the generation of BCR repertoire diversity during B cell development, as well as the mature BCR repertoire. Our analysis provides a window into the major processes involved in diversifying the B cell repertoire in control and Ezrin-deficient B cells, including V gene usage, number, frequency and length of unique CDR3s, nucleotide additions and trimming, and shared and unique clonotypes. Our data suggest that the Ezrin cytoskeleton in B cells impacts humoral immunity not only through modulation of B cell activation upon foreign antigen encounter, but also through qualitative and quantitative modulation of the available BCR repertoire.

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Fraley, Elizabeth R., Santosh Khanal, Stephen H. Pierce, Cas A. LeMaster, Rebecca McLennan, Tomi Pastinen et Todd Bradley. « Effects of Prior Infection with SARS-CoV-2 on B Cell Receptor Repertoire Response during Vaccination ». Vaccines 10, n^o 9 (6 septembre 2022) : 1477. http://dx.doi.org/10.3390/vaccines10091477.

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Understanding the B cell response to SARS-CoV-2 vaccines is a high priority. High-throughput sequencing of the B cell receptor (BCR) repertoire allows for dynamic characterization of B cell response. Here, we sequenced the BCR repertoire of individuals vaccinated by the Pfizer SARS-CoV-2 mRNA vaccine. We compared BCR repertoires of individuals with previous COVID-19 infection (seropositive) to individuals without previous infection (seronegative). We discovered that vaccine-induced expanded IgG clonotypes had shorter heavy-chain complementarity determining region 3 (HCDR3), and for seropositive individuals, these expanded clonotypes had higher somatic hypermutation (SHM) than seronegative individuals. We uncovered shared clonotypes present in multiple individuals, including 28 clonotypes present across all individuals. These 28 shared clonotypes had higher SHM and shorter HCDR3 lengths compared to the rest of the BCR repertoire. Shared clonotypes were present across both serotypes, indicating convergent evolution due to SARS-CoV-2 vaccination independent of prior viral exposure.

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Weng, Ruiqiang, Sudong Liu, Xiaodong Gu et Zhixiong Zhong. « Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes ». Open Life Sciences 16, n^o 1 (1 janvier 2021) : 884–98. http://dx.doi.org/10.1515/biol-2021-0091.

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Abstract Type 2 diabetes mellitus (T2DM) is known as a risk factor for coronary in-stent restenosis (ISR) in patients with coronary artery disease (CAD). Evidence suggests that B cells play a functional role in the progression of atherosclerotic lesions. However, the B cell receptor (BCR) repertoire in patients with ISR remains unclear. This study aims to profile the BCR repertoire in patients with coronary ISR/T2DM. A total of 21 CAD patients with or without ISR/T2DM were enrolled. PBMCs were isolated and examined for BCR repertoire profiles using DNA-seq. Our results showed that the diversity of amino acid sequences in ISR DM patients was higher than that in ISR −DM patients. The frequencies of 21 V/J paired genes differed between ISR DM and −ISR DM patients, while frequencies of 5 V/J paired genes differed between ISR DM and ISR −DM. The −ISR −DM group presented the highest clonotype overlap rate, while ISR DM patients presented the lowest overlap rate. Our study presented the BCR repertoires in patients with ISR/T2DM. The data suggested different BCR signatures between patients with ISR and T2DM. Further analysis of BCR profiles would enhance understanding of ISR.

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Krishna, Chirag, et A. Ari Hakimi. « Rules of Engagement : The Lymphocyte Receptor Ecosystem in Renal Cell Carcinoma ». Cancer Research 82, n^o 5 (1 mars 2022) : 764–65. http://dx.doi.org/10.1158/0008-5472.can-22-0146.

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Immune receptor repertoires provide insight into the clonal distribution of tumor-infiltrating lymphocytes, yet the clinical implications of T-cell receptor (TCR) and B-cell receptor (BCR) repertoire diversity in cancer are unclear. In this issue of Cancer Research, Ferral-Fairbanks and colleagues reveal the interplay between repertoire diversity, tumor molecular features, and clinical outcome in renal cell carcinoma (RCC). The authors show that aggressive tumors harbor increasingly diverse TCR and BCR repertoires and that both repertoires are altered by common RCC driver mutations. Moreover, the authors demonstrate that high TCR diversity is associated with improved overall survival. This study highlights the contribution of lymphocyte receptor dynamics to the emerging complexity of RCC antitumor immune responses. See related article by Ferral-Fairbanks et al., p. 929

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Shi, Xiaodong, Tihong Shao, Feifei Huo, Chenqing Zheng, Wanyu Li et Zhenyu Jiang. « An analysis of abnormalities in the B cell receptor repertoire in patients with systemic sclerosis using high-throughput sequencing ». PeerJ 8 (14 janvier 2020) : e8370. http://dx.doi.org/10.7717/peerj.8370.

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Systemic sclerosis is a chronic multisystem autoimmune disease that is associated with polyclonal B cell hyperreactivity. The CDR3 of BCRs is the major site of antigen recognition. Therefore, we analyzed the BCR repertoire of patients with SSc. The BCR repertoires in 12 subjects including eight SSc patients and four healthy controls were characterized by high-throughput sequencing, and bioinformatics analysis were studied. The average CDR3 length in the SSc group was significantly shorter. The SSc patient displayed more diverse BCR. Moreover, SSc patients with mild skin sclerosis, anti-Scl70, interstitial lung disease or female sex were more diversified. B cells from the SSc patients showed a differential V and J gene usage. SSc patients had distinct BCR repertoires.These findings reflected the differences of BCR repertoires between SSc patients and controls. The higher-usage genes for the BCR sequence might be potential biomarkers of B cell-targeted therapies or diagnosis for SSc.

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de Bourcy, Charles F. A., Cesar J. Lopez Angel, Christopher Vollmers, Cornelia L. Dekker, Mark M. Davis et Stephen R. Quake. « Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging ». Proceedings of the National Academy of Sciences 114, n^o 5 (17 janvier 2017) : 1105–10. http://dx.doi.org/10.1073/pnas.1617959114.

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The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly individuals before and after influenza vaccination. We determined that BCR repertoires become increasingly specialized over a span of decades, but less plastic. In 50% of the elderly individuals, a large space in the repertoire was occupied by a small number of recall lineages that did not decline during vaccine response and contained hypermutated IgD+B cells. Relative to their younger counterparts, older subjects demonstrated a contracted naive repertoire and diminished intralineage diversification, signifying a reduced substrate for mounting novel responses and decreased fine-tuning of BCR specificities by somatic hypermutation. Furthermore, a larger proportion of the repertoire exhibited premature stop codons in some elderly subjects, indicating that aging may negatively affect the ability of B cells to discriminate between functional and nonfunctional receptors. Finally, we observed a decreased incidence of radical mutations compared with conservative mutations in elderly subjects’ vaccine responses, which suggests that accumulating original antigenic sin may be limiting the accessible space for paratope evolution. Our findings shed light on the complex interplay of environmental and gerontological factors affecting immune senescence, and provide direct molecular characterization of the effects of senescence on the immune repertoire.

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Forgacs, David, Rodrigo B. Abreu, Giuseppe A. Sautto, Greg A. Kirchenbaum, Elliott Drabek, Kevin S. Williamson, Dongkyoon Kim, Daniel E. Emerling et Ted M. Ross. « Convergent antibody evolution and clonotype expansion following influenza virus vaccination ». PLOS ONE 16, n^o 2 (22 février 2021) : e0247253. http://dx.doi.org/10.1371/journal.pone.0247253.

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Recent advances in high-throughput single cell sequencing have opened up new avenues into the investigation of B cell receptor (BCR) repertoires. In this study, PBMCs were collected from 17 human participants vaccinated with the split-inactivated influenza virus vaccine during the 2016–2017 influenza season. A combination of Immune Repertoire Capture (IRCTM) technology and IgG sequencing was performed on ~7,800 plasmablast (PB) cells and preferential IgG heavy-light chain pairings were investigated. In some participants, a single expanded clonotype accounted for ~22% of their PB BCR repertoire. Approximately 60% (10/17) of participants experienced convergent evolution, possessing public PBs that were elicited independently in multiple participants. Binding profiles of one private and three public PBs confirmed they were all subtype-specific, cross-reactive hemagglutinin (HA) head-directed antibodies. Collectively, this high-resolution antibody repertoire analysis demonstrated the impact evolution can have on BCRs in response to influenza virus vaccination, which can guide future universal influenza prophylactic approaches.

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Zhang, Li, Harini Kandadi, Alan Paciorek, Nancy N. Chang, Nadeem Anwar Sheikh et Lawrence Fong. « Tracking of long-term B-cell memory responses using B-cell receptor (BCR) sequencing in prostate cancer (PC) patients (pts) treated with sipuleucel-T (sip-T). » Journal of Clinical Oncology 36, n^o 6_suppl (20 février 2018) : 309. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.309.

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309 Background: Sip-T is an autologous cellular immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sip-T’s induction of B-cell responses to PAP and other antigens correlates with improved survival (Sheikh 2013, GuhaThakurta 2015). Cancer vaccine-induced changes to BCR repertoire are unknown. To assess changes in BCR repertoire upon booster treatment, we compared patients retreated with sip-T (P10-1) to treatment-naïve patients (STRIDE). Methods: STRIDE pts (N = 52) received sip-T with concurrent or sequential enzalutamide for mCRPC (Petrylak 2015). P10-1 pts (N = 8) previously treated with sip-T for androgen-dependent PC were retreated with a booster course for mCRPC, after a median of 8.9 years (Beer 2017). Blood samples were collected at baseline (wk 0) and during (wk 2, 4)/post-sip-T (wk 6, 26, 52). Deep sequencing was performed using the ImmunoSEQ assay (Adaptive Biotechnologies). BCR diversity was assessed by clonality, and BCR dynamics by fold-change analysis (Zhang 2017). Results: BCR repertoire had significantly higher clonality in P10-1 vs STRIDE (wk 0: p = 0.003, wk 2: p < 0.001, wk 4: p < 0.001), suggestive of a more focused BCR repertoire. P10-1 also showed increased clonality from wk 0 to 4 (p = 0.063), whereas STRIDE showed a significant increase in clonality from wk 0 to 6 (p = 0.039), suggesting that BCR repertoire focused earlier in P10-1. Starting at wk 2, more clones remained in the repertoire in P10-1, indicating that sip-T stimulated immunologic memory early, after 1st retreatment (p < 0.05). There was less change over time (clonal shuffling) within the 100 most abundant baseline clones in P10-1 (p = 0.080), suggesting more relevant clones preexisted at baseline and enriched over time. After the first two sip-T infusions, more clones contracted in P10-1 (p = 0.027, p = 0.014), whereas more new clones were generated in STRIDE (p = 0.083, p = 0.003). Conclusions: Sip-T induces long-lasting changes in the BCR repertoire. Sip-T retreatment leads to quicker focusing of BCR repertoire than initial treatment. These results are consistent with sip-T inducing durable immunologic memory.

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Zhang, Ruoxi, Junling Zhuang et Bing HAN. « Exploration of B and T Cell Receptor Repertoires Reveals Distinct Mechanisms in Pure Red Cell Aplasia, Autoimmune Hemolytic Anemia, and Aplastic Anemia ». Blood 142, Supplement 1 (28 novembre 2023) : 5196. http://dx.doi.org/10.1182/blood-2023-174862.

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Background: Pure red cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA) and aplastic anemia (AA) are immune-mediated diseases that mainly attack erythrocyte or erythroid progenitor cells. This study aimed to investigate changes related to autoimmunity in the B cell receptor (BCR) and T cell receptor (TCR) repertoires in these diseases. Methods: Patients with newly diagnosed primary PRCA, AIHA, and AA and healthy individuals with matched age and sex (normal controls, NC) were recruited. Peripheral blood was collected, and BCR and TCR repertoires were sequenced by next-generation immunosequencing. The diversity and clonal expansion of the repertoires, gene and gene combination usage, somatic hypermutation (SHM) of BCR, and the sequence length, hydrophobicity, motifs of the most diverse epitope encoded (complementary-determining region 3, CDR3), T cell clustering, and BCR light chain and TCRα chain were analyzed. Results: 10 PRCA, 10 AIHA, 10 AA, and 7 NC were finally enrolled. For the broad repertoire metrics analysis, only the TCR repertoire of the AA group was more diverse compared with NC (p＜0.05). For BCR and TCR repertoires, PRCA, AIHA, and AA showed uniform characteristics in gene usage. The preferential gene usage of PRCA immunoglobulin heavy (IGH) chains such as IGHV3-23, IGHV3-74 were correlated with memory cells and red blood cell antigen recognition; the higher usage of IGHV4-31 in the AIHA group was associated with secretion of auto-antibodies; whereas AA patients had more gene usage of neutralizing antibodies (p＜0.05). In the gene usage in T cell receptor β (TRB) chains, PRCA patients had skewed usage of genes associated with T cell dysregulation and hyperinflammation such as TRBV1 and TRBV11-2; the increased gene usage in AIHA and AA were also found in other autoimmune diseases, which correlated with abnormal antigen recognition. PRCA and AA also had specific TRBV-J gene combination usage. Only PRCA had higher BCR SHM compared with NC (p＜0.05). The length of CDR3 was similar but the hydrophobicity was different among different disease groups. 12, 28, and 22 motifs were found respectively in BCR of PRCA, AIHA, and AA; and 13, 6, and 6 motifs were found in TCR. Compared with NC, PRCA, AIHA, and AA showed a considerable lack of physiology T cell clusters, and 147, 98, and 141 disease-specific T cell clusters in each disease was found, respectively. For light chain of BCR, PRCA and AIHA had the tendency of more usage of κ chains, whereas AA had more usage of λ chains. For TCRα chains, the three diseases used more genes related to hypersensitivity reactions (p＜0.05). Conclusion: PRCA, AIHA, and AA had different BCR and TCR repertoire characteristics in gene and gene combination usage, hydrophobicity and motifs of CDR3, and T cell clustering, which might contribute to autoimmune antigen recognition. The abnormalities were mainly T cell-related for PRCA, B cell-related for AIHA and both for AA. Keywords: pure red cell aplasia; autoimmune hemolytic anemia; aplastic anemia; BCR; TCR

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Thèses sur le sujet "BCR repertoire"

Abdollahi, Nika. « B cell receptor repertoire analysis in clinical context : new approaches for clonal grouping, intra-clonal diversity studies, and repertoire visualization ». Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS063.

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Le séquençage de nouvelle génération a permis aux chercheurs de réaliser des analyses approfondies du paysage du répertoire immunologique. Cependant, une préoccupation importante dans ces études est le coût informatique de l'analyse de millions de séquences avec une complexité, une variabilité et une capacité de mutation inhérentes, imposant des défis informatiques et nécessitant le développement de méthodes efficaces. Ce défi est encore plus évident dans le contexte clinique qui n'a pas nécessairement accès à des professionnels ayant des compétences informatiques ou des ressources informatiques robustes. Ainsi, l'objectif principal de cette thèse est de développer un ensemble d'outils dédiés qui seront utilisés dans l'environnement clinique, pour le diagnostic médical et les soins aux patients, et dans l'environnement de recherche, pour effectuer une analyse approfondie et à grande échelle du répertoire. Nous avons conçu et implémenté de multiples algorithmes et les avons rassemblés dans un pipeline interactif de visualisation du répertoire BCR afin de faciliter le processus d'intégration de l'analyse du répertoire BCR dans les pratiques médicales
Next-generation sequencing has enabled researchers to conduct in-depth analyses of the immunological repertoire landscape. However, a significant concern in these studies is the computational cost of analyzing millions of sequences with inherent complexity, variability, and mutational capacity, imposing computational challenges and necessitating the development of efficient methods. This challenge is even more evident in the clinical context that does not necessarily have access to professionals with computing skills or robust computational resources. Thus, the main goal of this thesis is to develop a set of dedicated and integrated tools to be used in the clinical environment, for medical diagnostic and patient care, and in the research environment, to perform large-scale and in-depth repertoire analysis. We have designed and implemented multiple algorithms and gathered them in a user-friendly interactive BCR repertoire visualization pipeline to facilitate the process of integrating BCR repertoire analysis into medical practices

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Fonte, Coralie. « Effets de différents modèles de stress sur le développement lymphocytaire ». Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0185/document.

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Les vols spatiaux sont source de nombreux stress conduisant à un affaiblissement du système immunitaire. L’efficacité de ce système repose notamment sur la diversité des répertoires de récepteurs aux antigènes présents à la surface des lymphocytes B (BCR) et T (TCR) permettant de reconnaitre un grand nombre d’antigènes différents. Au cours de cette thèse, j’ai étudié la diversité des récepteurs à l’antigène dans trois modèles animaux différents : l’amphibien Pleurodeles waltl, le modèle murin de suspension anti‐orthostatique (micropesanteur simulée) et le modèle murin CUMS (pour « Chronic Unpredictable Mild Socio‐environmental stressors ») qui fait appel à des stress sociaux et environnementaux chroniques similaires à ceux rencontrés lors des vols spatiaux. L’étude des répertoires de chaînes lourdes d’anticorps IgM et IgY de P. waltl a montré que ceux‐ci présentent une diversité importante, faisant de cet animal un bon modèle pour étudier les effets d’un vol spatial sur le système immunitaire humoral. Nous avons aussi montré que l’exposition à la suspension anti‐orthostatique durant 21 jours diminue la lymphopoïèse B mais n’affecte que modérément la diversité du répertoire de chaînes lourdes d’IgM. Ces résultats ont été comparés à ceux obtenus avec des souris âgées afin de savoir si la suspension anti‐orthostatique induit un vieillissement accéléré du système immunitaire. Même si nous avons noté des similitudes intéressantes entre ces deux groupes de souris, nous avons constaté que l’effet du vieillissement sur le répertoire d’IgM est plus important que celui de la suspension anti‐orthostatique, suggérant que le temps d’exposition au modèle anti‐orthostatique devrait être augmenté pour accentuer ses effets sur le répertoire d’anticorps. Quant au modèle CUMS, nous avons montré que son application durant la gestation n’impacte pas la lymphopoïèse T chez les souriceaux nouveau‐nés mais affecte 25% de leur répertoire de chaînes lourdes β du TCR. Ces résultats suggèrent que des stress socio‐environnementaux chroniques, même de faibles intensités, pourraient modifier les capacités de reconnaissance antigénique de l’hôte
Spaceflight is a source of various stresses leading to the weakening of the immune system. The efficiency of this system relies, notably, on the diversity of antigen receptor repertoires present on B (BCR) and T (TCR) cells, allowing the recognition of a vast array of antigens. During this thesis, I studied the diversity of antigen receptors in three different animal models: the amphibian Pleurodeles waltl, the murine anti‐orthostatic suspension model (simulated microgravity) and the CUMS (for "Chronic Unpredictable Mild Socio‐environmental stressors") murine model involving exposure to chronic social and environmental stressors similar to those encountered during spaceflights. Analyses of P. waltl IgM and IgY heavy chain repertoires have shown that they are highly diverse, making this species a nice animal model for studying the effects of spaceflight on the humoral immune system. We have also shown that 21 days of anti‐orthostatic suspension decrease murine B lymphopoiesis and moderately affect IgM heavy chain repertoire diversity. These results were compared with those obtained with old mice to determine if anti‐orthostatic suspension induces an accelerated aging of the immune system. Although we noted interesting similarities between these two groups of mice, we found that the effect of aging on IgM repertoire is stronger than that of the anti‐orthostatic suspension, suggesting that anti‐orthostatic duration should be extended to increase the effects of this model on antibody repertoire. Finally, regarding the CUMS model, we have shown that, when applied during gestation it does not affect T lymphopoiesis in newborn mice but affects 25% of their TCRβ heavy chain repertoire. These results suggest that low‐intensity chronic socio‐environmental stressors may alter antigen recognition capabilities of the host

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Papadopoulou, Maria. « Thymic development and peripheral functional polarisation of human Vγ9Vδ2 T cells ». Doctoral thesis, Universite Libre de Bruxelles, 2020. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/304309.

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Vγ9Vδ2 T cells are a subset of human T lymphocytes activated by phosphoantigens in a T cell receptor-dependent manner to fight microbial invaders or kill transformed cells. Phosphoantigens are low molecular weight nonpeptidic pyrophosphate containing metabolites produced both endogenously (upregulated in transformed cells) and by microbes. Vγ9Vδ2 T cells are the first T cells generated in the foetus and have programmed functions before encountering the post-partum environment.In this PhD thesis, the aim was to assess the origin of Vγ9Vδ2 T cells in early versus adult life and to evaluate their T cell receptor repertoire and effector potential in the neonatal and infant period. First, human Vγ9Vδ2 T cells were characterised coming from foetal blood and generated by the foetal thymus and then similarities and differences with adult blood Vγ9Vδ2 T cells were identified. The data showed that there is a post-natal thymic output of Vγ9Vδ2 T cells which are different from their foetal counterparts. This finding could help guide the development of cancer immunotherapy strategies aiming to improve the resistance and tenacity of Vγ9Vδ2 T cells which enter an exhaustion state after long encounter with the antigen.Furthermore, human Vγ9Vδ2 T cells were studied early after birth regarding their T cell receptor repertoire and function. At 10 weeks after birth, Vγ9Vδ2 T cells had expanded, and a big part of the Vγ9Vδ2 T cell repertoire was foetal-derived. Additionally, Vγ9Vδ2 T cells had undergone significant functional polarisation toward potent killer effector cells. The expansion and shift in effector functions were not influenced by neonatal BCG vaccination, highlighting the role of environmental exposure upon birth. The data gathered here highlight the unique properties of this innate-like lymphocyte population which can act as a first wave of protection in early life while conventional αβ T cells are not yet optimal. Later in life, another wave of Vγ9Vδ2 T cells arrives from the thymus to expand and populate the adult periphery, providing a possible avenue of new and robust cancer cell killers in the scope of immunotherapy.
Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished

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Livres sur le sujet "BCR repertoire"

Pisa, Università di, dir. Syrian and Phoenician ivories of the early first millennium BCE : Chronology, regional styles and iconographic repertories, patterns of inter-regional distribution. Pisa : Edizioni ETS, 2009.

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Cracknell, H. L. New Catering Repertoire : Part I : The Headwaiter's Handbook : Part II : Wine and Waiting Bar Man (New Catering Repertoire). Van Nostrand Reinhold, 1991.

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Polis, Stéphane. The Scribal Repertoire of Amennakhte Son of Ipuy. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198768104.003.0005.

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This chapter investigates linguistic variation in the texts written by the Deir el-Medina scribe Amennakhte son of Ipuy in New Kingdom Egypt (Twentieth Dynasty; c. 1150 BCE). After a discussion of the challenge posed by the identification of scribes and authors in this sociocultural setting, I provide an overview of the corpus of texts that can tentatively be linked to this individual and justify the selection that has been made for the present study. The core of this paper is then devoted to a multidimensional analysis of Amennakhte’s linguistic registers. By combining the results of this section with a description of Amennakhte’s scribal habits—both at the graphemo-morphological and constructional levels—I test the possibility of using ‘idiolectal’ features to identify the scribe (or the author) of other texts stemming from the community of Deir el-Medina and closely related to Amennakhte.

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Shehata, Dahlia. Musiker und ihr vokales Repertoire : Untersuchungen zu Inhalt und Organisation von Musikerberufen und Liedgattungen in altbabylonischer Zeit. Universitätsverlag Göttingen, 2009.

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Barmash, Pamela. The Laws of Hammurabi. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780197525401.001.0001.

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The Laws of Hammurabi is one of the earliest law codes, dating from the eighteenth century BCE Mesopotamia (ancient Iraq). It is the culmination of a tradition in which scribes would demonstrate their legal flair by composing statutes on a repertoire of traditional cases, articulating what they deemed just and fair. The book describes how the scribe of the Laws of Hammurabi advanced beyond earlier scribes in composing statutes that manifest systematization and implicit legal principles. The scribe inserted the statutes into the structure of a royal inscription, skillfully reshaping the genre. This approach allowed the king to use the law code to demonstrate that Hammurabi had fulfilled the mandate to guarantee justice enjoined upon him by the gods, affirming his authority as king. This tradition of scribal improvisation on a set of traditional cases continued outside of Mesopotamia, influencing biblical law and the law of the Hittite Empire and perhaps shaping Greek and Roman law. The Laws of Hammurabi is also a witness to the start of another stream of intellectual tradition. It became a classic text and the subject of formal commentaries, marking a Copernican revolution in intellectual culture.

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Waters, Keith. Postbop Jazz in the 1960s. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780190604578.001.0001.

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Innovations in postbop jazz compositions of the 1960s occurred in several dimensions, including harmony, form, and melody. Postbop jazz composers such as Wayne Shorter, Herbie Hancock, Chick Corea, along with others (Booker Little, Joe Henderson, Woody Shaw) broke with earlier tonal jazz traditions. Their compositions marked a departure from the techniques of jazz standards and original compositions that defined small-group repertory through the 1950s: single-key orientation, schematic 32-bar frameworks (in AABA or ABAC forms), and tonal harmonic progressions. The book develops analytical pathways through a number of compositions, including “El Gaucho,” “Penelope,” “Pinocchio,” “Face of the Deep” (Shorter); “King Cobra,” “Dolphin Dance,” “Jessica” (Hancock); “Windows,” “Inner Space,” “Song of the Wind” (Corea); as well as “We Speak” (Little); “Punjab” (Henderson); and “Beyond All Limits” (Shaw). These case studies offer ways to understand the works’ harmonic syntax, melodic and formal designs, and general principles of harmonic substitution. By locating points of contact among these postbop techniques—and by describing their evolution from previous tonal jazz practices—the book illustrates the syntactic changes that emerged during the 1960s.

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Chapitres de livres sur le sujet "BCR repertoire"

Cracknell, H. L., et G. Nobis. « Bar and Cellar Operation ». Dans The New Catering Repertoire, 384–92. London : Macmillan Education UK, 1990. http://dx.doi.org/10.1007/978-1-349-21007-7_16.

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Natvig, Jacob B., Kay B. Wilson, Alison Quayle, Sel Suleyman, Jens Kjeldsen-Kragh, Øystein Førre, Mouldy Sioud et J. Donald Capra. « T cell receptor variable gene repertoire in rheumatoid synovial T cells responding to BCG ». Dans Autoimmunity : Experimental Aspects, 191–96. Berlin, Heidelberg : Springer Berlin Heidelberg, 1994. http://dx.doi.org/10.1007/978-3-642-78779-9_15.

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Chittick, Andrew. « The Buddhist Repertoire, Part 1 ». Dans The Jiankang Empire in Chinese and World History, 269–94. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780190937546.003.0012.

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Chapter 10, “The Buddhist Repertoire, Part 1: The Era of Pluralist Patronage,” is the first half of the third study of various repertoires of political legitimation. This chapter focuses on the development of Buddhist institutions and historiography in the fifth century, a period of pluralist patronage under the banner of Sinitic universalism. The Buddhist repertoire in maritime diplomatic relations with South Seas regimes proved an important staging ground for the ruler’s performance as a cakravartin, or Buddhist universal ruler, as well as a conduit for Buddhist expertise. By the end of the fifth century, Jiankang elites had developed Buddhist legends and practices that asserted that the Jiankang regime’s legitimacy derived, not from the Han Empire, but from its direct inheritance of legitimacy from the cakravartin Asoka, who had ruled in northern India in the third century BCE. This set the stage for the striking developments of the sixth century.

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Demetriou, Denise. « The Adaptive Repertoires of Immigrants ». Dans Phoenicians among Others, 15—C1P44. Oxford University PressNew York, 2023. http://dx.doi.org/10.1093/oso/9780197634851.003.0002.

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Abstract This chapter explores the lives of individual Phoenician immigrants in three Greek city-states over three centuries, through an examination of primarily bilingual inscriptions on tombstones from fourth-century bce Athens, third-century bce Demetrias in Thessaly, and second-century bce Rhodes. The evidence illustrates how these immigrants coped with migration and reveals similarities across time and space in the adaptive strategies that Phoenician immigrants adopted to facilitate their lives as immigrants and encourage a sense of belonging in their new homes. The chapter discusses three main strategies—name changing, the adoption and incorporation of local customs into immigrants’ cultural practices, and immigrants’ eventual participation in the civic life of their host city. These adaptations allowed Phoenician immigrants to become better integrated into their new societies, despite their persistent use of the Phoenician language and script on both private and public monuments. Such integration, the chapter argues, was a two-way process that involved both the migrants’ adaptive repertoires and the migration and membership regimes of the host states, eventually leading to the acceptance, inclusion, and incorporation of migrants into the civic bodies of their host states and a transformation of the migrants themselves.

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Manning, Jane. « At the Edge of Time (1982) Brian Elias (born 1948) Text by Mervyn Peake ». Dans New Vocal Repertory, 203–6. Oxford University PressOxford, 1994. http://dx.doi.org/10.1093/oso/9780198164135.003.0061.

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Abstract The composer’s beautifully bold handwriting instantly encourages the performer. The refinement and delicacy characteristic of his music is at once apparent. Such meticulous details of nuance and accent and flexible and subtle rhythms demand dedication from the singer, who will be amply rewarded. Bar-lines are omitted in the third song and again at the very end of the cycle, but conventional notation is otherwise used. The musical idiom is atonal, but constant repetition of intervals and pitch cells are a good means of orientation for singers worried by intonation problems. The dramatic scope is very wide indeed. This is a superb vehicle for a tenor of high musicianship and powerful presence.

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Seroussi, Edwin. « New Directions in the Music of the Sephardic Jews Edwin Seroussi (bar-ilan university) ». Dans Modern jews and their musical agendas, 61–77. Oxford University PressNew York, NY, 1994. http://dx.doi.org/10.1093/oso/9780195086171.003.0004.

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Abstract The redefinition of meaning and content in a musical tradition exposed to radical new circumstances does not necessarily imply the extinction of its identity but rather its power to revitalize itself. In discussing the social and cultural transformations affecting the Sephardic Jews since the mid-nineteenth century, several authors have raised the likelihood of the eventual disappearance of vital portions of their musical traditions.1 As indicated in its title, this article takes an alternative point of view. The phrase “new directions” assumes a departure from established patterns of musical creativity and behavior, not necessarily confined to the renewal of musical materials (e.g., new melodies added to the repertory), but also including changes in music appreciation, aesthetic values, performance practices and the social functions of music. Such changes, however, may be seen as part of a dynamic process in which music rooted in traditional repertories continues to be one of the most salient features contributing to the maintenance of a worldwide Sephardic Jewish identity.

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Manning, Jane. « PETER ASTON (1938–2013)Five Songs of Crazy Jane (1960) ». Dans Vocal Repertoire for the Twenty-First Century, Volume 1, 22–25. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780199391028.003.0007.

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This chapter describes the first acknowledged work of Peter Aston, Crazy Jane. Here, Crazy Jane, now a raddled hag, recalls the lusty passions of her youth, reflecting bitterly on the cruel reality of spent beauty. This is a dramatic scena with strong elements of folk song that can give the performer a chance to demonstrate vocal quality, flair, and musicianship. Consistency of tonal centres and rhythmic patterns gives the music cohesion, and lines move effortlessly through a wealth of subtle modulations. The basically tonal idiom moreover does not create a difficult challenge for an inexperienced singer. Double bar-lines divide each of the five songs into further clear sections, forming a disciplined framework which should be apparent in performance.

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Manning, Jane. « HANS WERNER HENZE (1926–2012)Three Auden Songs (1983) ». Dans Vocal Repertoire for the Twenty-First Century, Volume 1, 125–27. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780199391028.003.0036.

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This chapter studies songs for the tenor repertoire by Hans Werner Henze. Henze’s three songs, based on texts by the poet W. H. Auden, are a key example of his fastidious and beautifully-crafted vocal writing. Henze sets these three contrasting poems with utmost sensitivity. The fast-moving texts contain layers of subtlety, couched in a concise, freely chromatic musical language which sits easily in the voice. The settings build cumulatively in proportion and weight. A tiny, poignant tribute to a dead cat leads to a powerfully intuitive, four-verse portrait of the poet Arthur Rimbaud. This is followed by a substantial love song, full of tenderness and passion, yet controlled with consummate skill. The work is written in standard notation (without bar-lines) and should prove a rewarding vehicle for singers of relatively modest attainment as well as mature artists.

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Manning, Jane. « COLIN MATTHEWS (b. 1946)Out in the Dark (2008) ». Dans Vocal Repertoire for the Twenty-First Century, Volume 2, 146–47. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780199390960.003.0046.

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This chapter addresses British composer Colin Matthews’s Out in the Dark (2008). This little song is but a modest sample of Matthews’s work, which covers virtually all genres. The piece’s tessitura means it can be tackled by most voices, since extremes of register and dynamic are avoided. In view of the buoyancy of timbre required, and the crucial instruction semplice, a soprano is most suitable, able to float a sweet ‘silvered’ sound with a distinctively bright sheen such as often found in singers of French songs. The tone can be ‘pure’ in the widest sense, but definitely not devoid of expression or vibrato or affectedly naïve. Apart from the initial pianissimo, no dynamics are marked, and this represents a challenge to the poise and powers of concentration of both performers. The voice part moves steadily through the work in unadorned lines, with a natural, lilting one-in-a bar feel, made more flexible by the interplay of two against three.

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Manning, Jane. « JOEL FEIGIN (b. 1951)Two Songs from ‘Twelfth Night’ (2013) ». Dans Vocal Repertoire for the Twenty-First Century, Volume 2, 72–74. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780199390960.003.0024.

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This chapter focuses on Joel Feigin’s Two Songs from ‘Twelfth Night’ (2013). This is but a small and relatively simple example of Feigin’s work, which embraces a great variety of styles and genres, and exhibits unfailingly high standards of professionalism and versatility. These settings of two well-loved Shakespeare texts have been extracted from his two-act opera, Twelfth Night. They make a pleasing concert item, suited to a light baritone who is happy sustaining cantabile lines which are sometimes exposed at key moments. The writing is, in general, lyrical and smooth, and proceeds in a straightforward, often identifiably tonal idiom, with just a few corners where pitches can deceive, especially in enharmonic relationships. Both settings are basically minuets—the first lithe and graceful, the second with a more sombre tread to its three-in-a-bar. Both also have slow codas which put the singer’s tonal steadiness under the microscope. Meanwhile, the piano parts veer between a lean sprightliness and warmer, shifting chordal chromaticism, supporting the voice with sensitivity at all times.

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Actes de conférences sur le sujet "BCR repertoire"

Zelazowska, Monika, Somnath Paul, Joshua Plummer, Manoj Chelvanambi, Beth Helmink, Russell Witt, Michael White et al. « 988 B-cell receptor (BCR) repertoire and antibody recognition analysis of melanoma patients treated with neoadjuvant immune checkpoint blockade (ICB) ». Dans SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.0988.

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Nassif, Elise, Bin Liu, Wei-Lien Wang, Alexander Lazar, Davis Ingram, Khalida Wani, Sheila Duncan et al. « 542 B-cell receptor (BCR) repertoire is a dynamic biomarker of survival in sarcoma patients treated with neoadjuvant immune checkpoint blockade (ICB) ». Dans SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.0542.

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Wang, Yue, et Michael T. Lotze. « Abstract 3963 : Deep serial analysis of the TCR/BCR CDR3 adaptome repertoire in peripheral blood of pancreatic cancer patients in a randomized study of neoadjuvant chemotherapy with or without autophagy inhibition ». Dans Proceedings : AACR Annual Meeting 2019 ; March 29-April 3, 2019 ; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-3963.

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Barbone, Dario, Dean A. Fennell et V. Courtney Broaddus. « Abstract B31 : Multicellular resistance to bortezomib acquired by mesothelioma spheroids can be reversed by modulation of the Bcl‐2 repertoire ». Dans Abstracts : AACR-NCI-EORTC International Conference : Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009 ; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-b31.

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