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https://www.readbyqxmd.com/read/28542921/cd40-mediated-signaling-influences-trafficking-tcr-expression-and-t-cell-pathogenesis-in-the-nod-model-of-type-1-diabetes
#1
Gisela M Vaitaitis, Dan M Waid, Martin G Yussman, David H Wagner
CD40 plays a critical role in the pathogenesis of type 1 diabetes (T1D). The mechanism of action however is undetermined, likely because CD40 expression has been grossly underestimated. CD40 is expressed on numerous cell types that now include T cells and pancreatic β cells. CD40(+) CD4(+) cells (TH40) prove highly pathogenic in NOD mice and in translational human T1D studies. We generated BDC2.5.CD40(-/-) and re-derived NOD.CD154(-/-) mice to better understand CD40 mechanism of action. Fully functional CD40 expression is required not only for T1D development but for insulitis...
May 19, 2017: Immunology
https://www.readbyqxmd.com/read/28535950/aging-related-changes-in-human-t-cell-repertoire-over-20years-delineated-by-deep-sequencing-of-peripheral-t-cell-receptors
#2
Kengo Yoshida, John B Cologne, Kismet Cordova, Munechika Misumi, Mika Yamaoka, Seishi Kyoizumi, Tomonori Hayashi, Harlan Robins, Yoichiro Kusunoki
Recent deep sequencing studies on T-cell receptor (TCR) repertoire have provided robust data to characterize diversity of T-cell immune responsiveness to a wide variety of peptide antigens, including viral and tumor antigens. The human TCR repertoire declines with age, but this decline has not been fully investigated longitudinally in individuals. Using a deep sequencing approach, we analyzed TCRβ repertoires longitudinally over approximately 20years, with ages ranging from 23 to 50years at the start (23 to 65years overall), in peripheral-blood CD4 and CD8 T-cell populations that were collected and cryopreserved 3 times at intervals of approximately 10years from each of 6 healthy adults (3 men and 3 women)...
May 20, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28534993/analysis-of-the-cdr3-length-repertoire-and-the-diversity-of-t-cell-receptor-%C3%AE-and-%C3%AE-chains-in-swine-cd4-and-cd8-t-lymphocytes
#3
Chun-Yan Wang, Yong-Xiang Fang, Guo-Hua Chen, Huai-Jie Jia, Shuang Zeng, Xiao-Bing He, Yuan Feng, Shou-Jie Li, Qi-Wang Jin, Wen-Yu Cheng, Zhi-Zhong Jing
The T cell receptor (TCR) is a complex heterodimer that recognizes fragments of antigens as peptides and binds to major histocompatibility complex molecules. The TCR α and β chains possess three hypervariable regions termed complementarity determining regions (CDR1, 2 and 3). CDR3 is responsible for recognizing processed antigen peptides. Immunoscope spectratyping is a simple technique for analyzing CDR3 polymorphisms and sequence length diversity, in order to investigate T cell function and the pattern of TCR utilization...
May 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28533222/fractionated-radiation-therapy-stimulates-anti-tumor-immunity-mediated-by-both-resident-and-infiltrating-polyclonal-t-cell-populations-when-combined-with-pd1-blockade
#4
Simon J Dovedi, Eleanor J Cheadle, Amy Popple, Edmund Poon, Michelle Morrow, Ross Stewart, Erik Yusko, Catherine Sanders, Marissa Vignali, Ryan Emerson, Harlan Robins, Robert W Wilkinson, Jamie Honeychurch, Timothy Illidge
Purpose: Radiotherapy (RT) is a highly effective anti-cancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. RT is known to enhance tumor immunogenicity; however, the contribution and mechanisms of RT induced immune responses are unknown. <p>Experimental Design: The impact of low-dose fractionated RT (5 x 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing (NGS) of the T-cell receptor (TCR)-repertoire...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28532760/research-techniques-made-simple-high-throughput-sequencing-of-the-t-cell-receptor
#5
Tiago R Matos, Menno A de Rie, Marcel B M Teunissen
High-throughput sequencing (HTS) of the T-cell receptor (TCR) is a rapidly advancing technique that allows sensitive and accurate identification and quantification of every distinct T-cell clone present within any biological sample. The relative frequency of each individual clone within the full T-cell repertoire can also be studied. HTS is essential to expand our knowledge on the diversity of the TCR repertoire in homeostasis or under pathologic conditions, as well as to understand the kinetics of antigen-specific T-cell responses that lead to protective immunity (i...
June 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28514688/the-e-id-protein-axis-specifies-adaptive-lymphoid-cell-identity-and-suppresses-thymic-innate-lymphoid-cell-development
#6
Masaki Miyazaki, Kazuko Miyazaki, Kenian Chen, Yi Jin, Jacob Turner, Amanda J Moore, Rintaro Saito, Kenichi Yoshida, Seishi Ogawa, Hans-Reimer Rodewald, Yin C Lin, Hiroshi Kawamoto, Cornelis Murre
Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28510537/converging-evolution-leads-to-near-maximal-junction-diversity-through-parallel-mechanisms-in-b-and-t-cell-receptors
#7
Jennifer Israel Cohen, Jeroen Heijst, Jacob Glanville, Yoram Louzoun
T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3) genetic diversity is produced through multiple diversification and selection stages. Potential holes in the CDR3 repertoire were argued to be linked to immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no Dβ germline genetic diversity, and the question whether they can produce a diverse CDR3 repertoire emerges. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large scale sequencing are required...
May 16, 2017: Physical Biology
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#8
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#9
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28496352/identification-of-expanded-t-cell-clones-by-spectratyping-in-nonfunctioning-kidney-transplants
#10
Maria Cappuccilli, Gabriele Donati, Giorgia Comai, Olga Baraldi, Diletta Conte, Irene Capelli, Valeria Aiello, Andrea Pession, Gaetano La Manna
BACKGROUND: The aim of this study was the application of complementarity-determining region-3 spectratyping analysis to determine T-cell-repertoire complexity and to detect T-cell-clone expansion, as a measure of immune response in nonfunctioning kidney transplants (group hemodialysis-transplant [HD-Tx]), nontransplanted dialysis patients (group hemodialysis [HD]), and normal subjects as controls (group C). PATIENTS AND METHODS: Analysis of T-cell receptor (TCR) diversity by spectratyping was applied to peripheral blood samples collected from 21 subjects: eight in group HD-Tx, seven in group HD, and six in group C...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28481982/mcpas-tcr-a-manually-curated-catalogue-of-pathology-associated-t-cell-receptor-sequences
#11
Nili Tickotsky, Tal Sagiv, Jaime Prilusky, Eric Shifrut, Nir Friedman
Motivation: While growing numbers of T cell receptor (TCR) repertoires are being mapped by high-throughput sequencing, existing methods do not allow for computationally connecting a given TCR sequence to its target antigen, or relating it to a specific pathology. As an alternative, a manually-curated database can relate TCR sequences with their cognate antigens and associated pathologies based on published experimental data. Results: We present McPAS-TCR, a manually curated database of TCR sequences associated with various pathologies and antigens based on published literature...
May 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28474248/a-potential-role-for-staphylococcal-and-streptococcal-superantigens-in-driving-skewing-of-tcr-v%C3%AE-subsets-in-tonsillar-hyperplasia
#12
Fiona J Radcliff, Fiona Clow, Murali Mahadevan, James Johnston, Thomas Proft, Richard G Douglas, John D Fraser
The TCR Vβ repertoire from patients with recurrent tonsillitis and/or tonsillar hyperplasia was examined to determine whether the TCR Vβ composition is suggestive of local superantigen activity and if so, whether it is associated with the presence of superantigen producing bacteria. Tonsil specimens were cultured aerobically to allow identification and isolation of the bacterial pathogens Staphylococcus aureus and Group A Streptococcus. TCR Vβ subset analysis of tonsil leucocytes was performed by flow cytometry...
May 4, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28462532/cell-death-and-thymic-tolerance
#13
REVIEW
Stephen R Daley, Charis Teh, Daniel Y Hu, Andreas Strasser, Daniel H D Gray
The differentiation of hematopoietic precursors into the many functionally distinct T-cell types produced by the thymus is a complex process. It proceeds through a series of stages orchestrated by a variety of thymic microenvironments that shape the T-cell developmental processes. Numerous cytokine and cell surface receptors direct thymocyte differentiation but the primary determinant of cell fate is the engagement of the T-cell antigen receptor (TCR). The strength of the TCR signal and the maturation stage of the thymocyte receiving it can direct the various differentiation programs or, alternatively, end the process by inducing cell death...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28450864/specificity-privacy-and-degeneracy-in-the-cd4-t-cell-receptor-repertoire-following-immunization
#14
Yuxin Sun, Katharine Best, Mattia Cinelli, James M Heather, Shlomit Reich-Zeliger, Eric Shifrut, Nir Friedman, John Shawe-Taylor, Benny Chain
T cells recognize antigen using a large and diverse set of antigen-specific receptors created by a complex process of imprecise somatic cell gene rearrangements. In response to antigen-/receptor-binding-specific T cells then divide to form memory and effector populations. We apply high-throughput sequencing to investigate the global changes in T cell receptor sequences following immunization with ovalbumin (OVA) and adjuvant, to understand how adaptive immunity achieves specificity. Each immunized mouse contained a predominantly private but related set of expanded CDR3β sequences...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28429709/t-follicular-helper-and-t-follicular-regulatory-cells-have-different-tcr-specificity
#15
Ana Raquel Maceiras, Silvia Cristina Paiva Almeida, Encarnita Mariotti-Ferrandiz, Wahiba Chaara, Fadi Jebbawi, Adrien Six, Shohei Hori, David Klatzmann, Jose Faro, Luis Graca
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28423320/sequence-and-structural-analyses-reveal-distinct-and-highly-diverse-human-cd8-tcr-repertoires-to-immunodominant-viral-antigens
#16
Guobing Chen, Xinbo Yang, Annette Ko, Xiaoping Sun, Mingming Gao, Yongqing Zhang, Alvin Shi, Roy A Mariuzza, Nan-Ping Weng
A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8(+) TCR repertoires for two dominant viral epitopes: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL) of influenza A virus. The highly individualized repertoires (87-5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#17
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416603/high-throughput-immunogenetics-for-clinical-and-research-applications-in-immunohematology-potential-and-challenges
#18
Anton W Langerak, Monika Brüggemann, Frédéric Davi, Nikos Darzentas, Jacques J M van Dongen, David Gonzalez, Gianni Cazzaniga, Véronique Giudicelli, Marie-Paule Lefranc, Mathieu Giraud, Elizabeth A Macintyre, Michael Hummel, Christiane Pott, Patricia J T A Groenen, Kostas Stamatopoulos
Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, next-generation sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416602/antigen-receptor-galaxy-a-user-friendly-web-based-tool-for-analysis-and-visualization-of-t-and-b-cell-receptor-repertoire-data
#19
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Andrew P Stubbs, Mirjam van der Burg
Antigen Receptor Galaxy (ARGalaxy) is a Web-based tool for analyses and visualization of TCR and BCR sequencing data of 13 species. ARGalaxy consists of four parts: the demultiplex tool, the international ImMunoGeneTics information system (IMGT) concatenate tool, the immune repertoire pipeline, and the somatic hypermutation (SHM) and class switch recombination (CSR) pipeline. Together they allow the analysis of all different aspects of the immune repertoire. All pipelines can be run independently or combined, depending on the available data and the question of interest...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28409183/combination-of-il-10-and-il-2-induces-oligoclonal-human-cd4-t-cell-expansion-during-xenogeneic-and-allogeneic-gvhd-in-humanized-mice
#20
Sojan Abraham, Hua Guo, Jang-Gi Choi, Chunting Ye, Midhun Ben Thomas, Nora Ortega, Alok Dwivedi, N Manjunath, Guohua Yi, Premlata Shankar
IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly divergent immunostimulatory effects under certain conditions. We found high levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rγcnull (NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution in vivo, showing an initial delay, followed by rapid expansion. Further, compared to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival in most animals and completely protected ∼20% of mice from GVHD...
April 2017: Heliyon
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