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tcr repertoire

Kilian Schober, Veit R Buchholz, Dirk H Busch
During infections and cancer, the composition of the T-cell receptor (TCR) repertoire of antigen-specific CD8+ T cells changes over time. TCR avidity is thought to be a major driver of this process, thereby interacting with several additional regulators of T-cell responses to form a composite immune response architecture. Infections with latent viruses, such as cytomegalovirus (CMV), can lead to large T-cell responses characterized by an oligoclonal TCR repertoire. Here, we review the current status of experimental studies and theoretical models of TCR repertoire evolution during CMV infection...
May 2018: Immunological Reviews
Jeannine A Ott, Caitlin D Castro, Thaddeus C Deiss, Yuko Ohta, Martin F Flajnik, Michael F Criscitiello
Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deaminase (AID) and results in both point and tandem mutations that accumulate non-conservative amino acid replacements within complementarity-determining regions (CDRs)...
April 17, 2018: ELife
Keiichi Sakurai, Kazuyoshi Ishigaki, Hirofumi Shoda, Yasuo Nagafuchi, Yumi Tsuchida, Shuji Sumitomo, Hiroko Kanda, Akari Suzuki, Yuta Kochi, Kazuhiko Yamamoto, Keishi Fujio
OBJECTIVE: Shared epitope (SE) alleles are the most significant genetic susceptibility locus in rheumatoid arthritis (RA); however, their target populations in CD4+ T cells are not well elucidated. We analyzed the association between SE alleles and the T cell receptor (TCR) repertoire diversity of naive and memory CD4+ T cells using next-generation sequencing (NGS). METHODS: The TCR beta chains in naive and memory CD4+ T cells from the peripheral blood of 22 patients with RA and 18 age- and sex-matched healthy donors (HD) were analyzed by NGS...
April 15, 2018: Journal of Rheumatology
Petros Christopoulos, Marc A Schneider, Farastuk Bozorgmehr, Jonas Kuon, Walburga Engel-Riedel, Jens Kollmeier, Volker Baum, Thomas Muley, Philipp A Schnabel, Helge Bischoff, Christian Grohé, Monika Serke, Michael Thomas, Paul Fisch, Michael Meister
OBJECTIVES: This study was performed to evaluate for a potentially important role of T cells in the pathophysiology and treatment sensitivity of large cell neuroendocrine lung carcinoma (LCNEC), an orphan disease with poor prognosis and scarce data to guide novel therapeutic strategies. MATERIALS AND METHODS: We performed T-cell receptor (TCR) β-chain spectratyping on blood samples of patients treated within the CRAD001KDE37 trial (n = 35) using age-matched current or former (n = 11) and never smokers (n = 10) as controls...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Chun-Bing Chen, Riichiro Abe, Ren-You Pan, Chuang-Wei Wang, Shuen-Iu Hung, Yi-Giien Tsai, Wen-Hung Chung
Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs)...
2018: Journal of Immunology Research
Bin Shi, Long Ma, Xiaoyan He, Peipei Wu, Peng Wang, Xiaomei Wang, Rui Ma, Xinsheng Yao
The diversity of the T cell receptor (TCR) complementarity determining region 3 (CDR3) repertoire is the result of random combinations, insertions and deletions during recombination of the germline V, D and J gene fragments. During evolution, some human TCR beta chain variable (TRBV) pseudogenes have been retained. Many previous studies have focused on functional TRBV genes, while little attention has been given to TRBV pseudogenes. To describe the compositional characteristics of TRBV pseudogene rearrangements, we compared and analysed TRBV pseudogenes, TRBV open reading frames (ORFs) and functional TRBV genes via high-throughput sequencing of DNA obtained from the peripheral blood of 4 healthy volunteers and 4 patients...
April 12, 2018: Scientific Reports
Sarina Ravens, Julia Hengst, Verena Schlapphoff, Katja Deterding, Akshay Dhingra, Christian Schultze-Florey, Christian Koenecke, Markus Cornberg, Heiner Wedemeyer, Immo Prinz
Human γδ T cells can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation. This study aimed to understand the clonal distribution of γδ T cells in peripheral blood of chronic HCV patients and following HCV clearance by interferon-free direct-acting antiviral drug therapies. To this end, γδ T cell receptor (TCR) repertoires were monitored by mRNA-based next-generation sequencing. While the percentage of Vγ9+ T cells was higher in patients with elevated liver enzymes and a few expanded Vδ3 clones could be identified in peripheral blood of 23 HCV-infected non-cirrhotic patients, overall clonality and complexity of γδ TCR repertoires were largely comparable to those of matched healthy donors...
2018: Frontiers in Immunology
Shawn P Fahl, David L Wiest
No abstract text is available yet for this article.
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jin-Huan Cui, Ya-Bin Jin, Kai-Rong Lin, Ping Xiao, Xiang-Ping Chen, Ying-Ming Pan, Wei Lin, Zu-Chang Wu, Dong-Mei Guo, Xiao-Fan Mao, Chu-Ling Zhang, Wen-Lue Lian, Wei Luo
Ankylosing spondylitis (AS) is a chronic and progressive autoimmune disease affecting the invasion of the spine, sacroiliac joints and peripheral joints. T cells play a vital role in the underlying pathogenesis of AS, which mediated autoimmune and inflammatory responses via specific recognition of autoantigen peptides presented by susceptibility HLA. Antigen-specific T cells triggered by HLA/antigen complexes will undergo a massive expansion that forming an uneven T cell repertoire. To enhance our understanding of T-cell-mediated autoimmune in AS, we applied TCR β chains high-throughput sequencing to AS patients for in-depth TCR repertoire analysis...
March 31, 2018: Human Immunology
Helen M McGuire, Thomas S Watkins, Matthew Field, Sarah Taylor, Nao Yasuyama, Andrew Farmer, John J Miles, Barbara Fazekas de St Groth
The utility of T-cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination-activating gene (RAG)-1 or RAG-2 knockouts is frequently used to generate mice with a monoclonal T-cell repertoire. However, low level productive TCR rearrangement has been reported in RAG-deficient mice expressing transgenic TCRs. Using deep sequencing, we set out to directly examine and quantify the presence of these endogenous TCRs...
March 24, 2018: Immunology and Cell Biology
Kazuyoshi Takeda, Kazutaka Kitaura, Ryuji Suzuki, Yuki Owada, Satoshi Muto, Naoyuki Okabe, Takeo Hasegawa, Jun Osugi, Mika Hoshino, Takuya Tsunoda, Ko Okumura, Hiroyuki Suzuki
Therapeutic cancer peptide vaccination is an immunotherapy designed to elicit cytotoxic T-lymphocyte (CTL) responses in patients. A number of therapeutic vaccination trials have been performed, nevertheless there are only a few reports that have analyzed the T-cell receptors (TCRs) expressed on tumor antigen-specific CTLs. Here, we use next-generation sequencing (NGS) to analyze TCRs of vaccine-induced CTL clones and the TCR repertoire of bulk T cells in peripheral blood mononuclear cells (PBMCs) from two lung cancer patients over the course of long-term vaccine therapy...
March 22, 2018: Cancer Immunology, Immunotherapy: CII
Minglin Ou, Fengping Zheng, Xinzhou Zhang, Song Liu, Donge Tang, Peng Zhu, Jingjun Qiu, Yong Dai
Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics...
March 20, 2018: Molecular Medicine Reports
Martine J Kallemeijn, François G Kavelaars, Michèle Y van der Klift, Ingrid L M Wolvers-Tettero, Peter J M Valk, Jacques J M van Dongen, Anton W Langerak
Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to autoimmunity and cancer development at older age. Even though TCRαβ+ and TCRγδ+ T-cells follow similar paths of development involving V(D)J-recombination of TCR genes in the thymus, TCRγδ+ T-cells tend to be more subjected to peripheral rather than central selection...
2018: Frontiers in Immunology
Benjamin J Wolf, Jiyoung Elizabeth Choi, Mark A Exley
iNKT cells are a subset of innate-like T cells that utilize an invariant TCR alpha chain complexed with a limited repertoire of TCR beta chains to recognize specific lipid antigens presented by CD1d molecules. Because iNKT cells have an invariant TCR, they can be easily identified and targeted in both humans and mice via standard reagents, making this a population of T cells that has been well characterized. iNKT cells are some of the first cells to respond during an infection. By making different types of cytokines in response to different infection stimuli, iNKT cells help determine what kind of immune response then develops...
2018: Frontiers in Immunology
Taigo Kato, Tatsuo Matsuda, Yuji Ikeda, Jae-Hyun Park, Matthias Leisegang, Sachiko Yoshimura, Tetsuro Hikichi, Makiko Harada, Makda Zewde, Sho Sato, Kosei Hasegawa, Kazuma Kiyotani, Yusuke Nakamura
Neoantigens are the main targets of tumor-specific T cells reactivated by immune checkpoint-blocking antibodies or when using tumor-infiltrating T cells for adoptive therapy. While cancers often accumulate hundreds of mutations and harbor several immunogenic neoantigens, the repertoire of mutation-specific T cells in patients might be restricted. To bypass suboptimal conditions, which impede the reactivation of existing T cells or the priming of neoantigen-specific T cells in a patient, we employ T cells of healthy donors with an overlapping HLA repertoire to target cancer neoantigens...
February 16, 2018: Oncotarget
Mikhail V Pogorelyy, Anastasia A Minervina, Dmitriy M Chudakov, Ilgar Z Mamedov, Yuri B Lebedev, Thierry Mora, Aleksandra M Walczak
Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform repertoire-wide disease association studies of antigen receptor sequences. We developed a statistical framework for associating receptors to disease from only a small cohort of patients, with no need for a control cohort. Our method successfully identifies previously validated Cytomegalovirus and type 1 diabetes responsive TCR β sequences...
March 13, 2018: ELife
Kok Fei Chan, Benjamin S Gully, Stephanie Gras, Dennis X Beringer, Lars Kjer-Nielsen, Jonathan Cebon, James McCluskey, Weisan Chen, Jamie Rossjohn
Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+ TRAJ21+ -TRBV28+ TRBJ2-3+ and TRAV4+ TRAJ8+ -TRBV9+ TRBJ2-1+ ), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72 ...
March 12, 2018: Nature Communications
Esteban Arrieta-Bolaños, Pietro Crivello, Maximilian Metzing, Thuja Meurer, Müberra Ahci, Julie Rytlewski, Marissa Vignali, Erik Yusko, Peter van Balen, Peter A Horn, J H Frederik Falkenburg, Katharina Fleischhauer
T cell alloreactivity is mediated by a self-human leukocyte antigen (HLA)-restricted T cell receptor (TCR) repertoire able to recognize both structurally similar and dissimilar allogeneic HLA molecules (i.e., differing by a single or several amino acids in their peptide-binding groove). We hypothesized that thymic selection on self-HLA molecules could have an indirect impact on the size and diversity of the alloreactive response. To test this possibility, we used TCR Vβ immunophenotyping and immunosequencing technology in a model of alloreactivity between self-HLA selected T cells and allogeneic HLA-DPB1 (DPB1) differing from self-DPB1*04:02 by a single (DPB1*02:01) or several (DPB1*09:01) amino acids in the peptide-binding groove...
2018: Frontiers in Immunology
Kostas Patas, Anne Willing, Cüneyt Demiralay, Jan Broder Engler, Andreea Lupu, Caren Ramien, Tobias Schäfer, Christian Gach, Laura Stumm, Kenneth Chan, Marissa Vignali, Petra C Arck, Manuel A Friese, Ole Pless, Klaus Wiedemann, Agorastos Agorastos, Stefan M Gold
While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-sectional case-control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities ( n  = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject ( n  = 20)...
2018: Frontiers in Immunology
Chaofei Cheng, Bei Wang, Lei Gao, Jianmin Liu, Xinchun Chen, He Huang, Zhendong Zhao
Tuberculosis (TB) is a severe global threat to human health. The immune protection initiated by γδ T cells play an important role in mycobacterial infection. Vaccines for Mycobacterium tuberculosis (Mtb) based on γδ T cells provide a novel approach for TB control. In our previous studies, we found a preponderant complementarity-determining region 3 (CDR3) sequence of the γδ T cell receptor (TCR) in TB patients, and successfully identified a tuberculosis antigen that can effectively activate γδ T cells with a reverse genetic strategy...
March 2, 2018: Scientific Reports
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