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https://www.readbyqxmd.com/read/29209563/comparative-immunologic-characterization-of-autoimmune-giant-cell-myocarditis-with-ipilimumab
#1
Alexandre Reuben, Mariana Petaccia de Macedo, Jennifer McQuade, Aron Joon, Zhiyong Ren, Tiffany Calderone, Brandy Conner, Khalida Wani, Zachary A Cooper, Hussein Tawbi, Michael T Tetzlaff, Robert F Padera, Jean-Bernard Durand, Alexander J Lazar, Jennifer A Wargo, Michael A Davies
Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipilimumab treatment. Histological analysis of heart tissue demonstrated findings consistent with giant cell myocarditis (GCM). The immune infiltrate in the heart was largely comprised of CD4+ T cells, whereas the liver had very few T cells, and CD8+ T cells were predominant in the responding lung metastases...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29208744/severity-of-acute-infectious-mononucleosis-correlates-with-cross-reactive-influenza-cd8-t-cell-receptor-repertoires
#2
Nuray Aslan, Levi B Watkin, Anna Gil, Rabinarayan Mishra, Fransenio G Clark, Raymond M Welsh, Dario Ghersi, Katherine Luzuriaga, Liisa K Selin
Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this virus leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in severity, from a mild transient influenza-like illness to a prolonged severe syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross-reactive CD8 T-cell response between influenza virus A-M158 (IAV-M1) and EBV BMLF1280 (EBV-BM) could modulate the immune response to EBV and play a role in determining the severity of AIM in 32 college students...
December 5, 2017: MBio
https://www.readbyqxmd.com/read/29203769/three-distinct-developmental-pathways-for-adaptive-and-two-ifn-%C3%AE-producing-%C3%AE-%C3%AE-t-subsets-in-adult-thymus
#3
Terkild Brink Buus, Niels Ødum, Carsten Geisler, Jens Peter Holst Lauritsen
Murine γδ T cells include subsets that are programmed for distinct effector functions during their development in the thymus. Under pathological conditions, different γδ T cell subsets can be protective or can exacerbate a disease. Here we show that CD117, CD200 and CD371, together with other markers, identify seven developmental stages of γδ T cells. These seven stages can be divided into three distinct developmental pathways that are enriched for different TCRδ repertoires and exhibit characteristic expression patterns associated with adaptive (γδTn), IFN-γ-producing (γδT1) and IFN-γ/IL-4-co-producing γδ T cells (γδNKT)...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29187849/quantification-of-inter-sample-differences-in-t-cell-receptor-repertoires-using-sequence-based-information
#4
Ryo Yokota, Yuki Kaminaga, Tetsuya J Kobayashi
Inter-sample comparisons of T-cell receptor (TCR) repertoires are crucial for gaining a better understanding of the immunological states determined by different collections of T cells from different donor sites, cell types, and genetic and pathological backgrounds. For quantitative comparison, most previous studies utilized conventional methods in ecology, which focus on TCR sequences that overlap between pairwise samples. Some recent studies attempted another approach that is categorized into Poisson abundance models using the abundance distribution of observed TCR sequences...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29187588/cxcr3-cxcl10-axis-shapes-tissue-distribution-of-memory-phenotype-cd8-t-cells-in-nonimmunized-mice
#5
Cécile Alanio, Rosa Barreira da Silva, David Michonneau, Philippe Bousso, Molly A Ingersoll, Matthew L Albert
The preimmune repertoire consists of mature T lymphocytes that have not yet been stimulated in the periphery. Memory phenotype (MP) cells have been reported as part of the preimmune repertoire (i.e., T cells bearing memory markers despite lack of engagement with cognate Ag); however, little is known about their trafficking and function. In this study, we hypothesized that MP cells, naive to TCR stimulation, constitute a transient population that traffics to tissues during development. Using mutant and transgenic animals with a monospecific TCR, we discovered increased numbers of MP CD8+ T cells circulating in nonimmunized Cxcr3-/- and Cxcl10-/- mice compared with wild-type animals...
November 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29180535/radiotherapy-and-ctla-4-blockade-shape-the-tcr-repertoire-of-tumor-infiltrating-t-cells
#6
Nils-Petter Rudqvist, Karsten A Pilones, Claire Lhuillier, Erik Wennerberg, John-William Sidhom, Ryan O Emerson, Harlan S Robins, Jonathan Schneck, Silvia C Formenti, Sandra Demaria
Immune checkpoint inhibitors activate T cells to reject tumors. Unique tumor mutations are key T-cell targets, but a comprehensive understanding of the nature of a successful antitumor T-cell response is lacking. To investigate the T-cell receptor (TCR) repertoire associated with treatment success versus failure we used a well-characterized mouse carcinoma that is rejected by CD8 T cells in mice treated with radiotherapy (RT) and anti-CTLA-4 in combination, but not as monotherapy, and comprehensively analyzed tumor-infiltrating lymphocytes (TILs) by high-throughput sequencing of the TCRΒ CDR3 region...
November 27, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29176983/mucosal-associated-invariant-t-cells-new-insights-into-antigen-recognition-and-activation
#7
REVIEW
Xingxing Xiao, Jianping Cai
Mucosal-associated invariant T (MAIT) cells, a novel subpopulation of innate-like T cells that express an invariant T cell receptor (TCR)α chain and a diverse TCRβ chain, can recognize a distinct set of small molecules, vitamin B metabolites, derived from some bacteria, fungi but not viruses, in the context of an evolutionarily conserved major histocompatibility complex-related molecule 1 (MR1). This implies that MAIT cells may play unique and important roles in host immunity. Although viral antigens are not recognized by this limited TCR repertoire, MAIT cells are known to be activated in a TCR-independent mechanism during some viral infections, such as hepatitis C virus and influenza virus...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29176645/t-cell-receptor-%C3%AE-chains-display-abnormal-shortening-and-repertoire-sharing-in-type-1-diabetes
#8
Iria Gomez-Tourino, Yogesh Kamra, Roman Baptista, Anna Lorenc, Mark Peakman
Defects in T cell receptor (TCR) repertoire are proposed to predispose to autoimmunity. Here we show, by analyzing >2 × 108 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4+ T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s (CDR3), in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. High frequency of short CDR3s is also observed in unproductive TCRB sequences, which are not subjected to thymic culling, suggesting that the shorter CDR3s arise independently of positive/negative selection...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163767/immunology-repertoire-study-of-pulmonary-sarcoidosis-t-cells-in-cd4-cd8-pbmc-and-tissue
#9
Yingyun Fu, Yazhen Li, Lan Xu, Shengguo Liu, Minlian Wang, Lu Xiao, Song Liu, Yong Dai
Sarcoidosis is a systemic granulomatous disorder highly related with immune response. The diversity and stability of the immune system could be measured by hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (TCR). Here we used a combination of multiplex PCR and next-generation sequencing to conduct a good quality analysis of the T-cell receptor BV complementarity-determining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from 7 sarcoidosis patients and lung sarcoidosis tissue from 6 patients...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138980/cd28-neg-t-lymphocytes-of-a-melanoma-patient-harbor-tumor-immunity-and-a-high-frequency-of-germline-encoded-and-public-tcrs
#10
Hisayoshi Hashimoto, Marco Sterk, Karin Schilbach
Increased numbers of CD8(+)CD28(neg.) T cells have been detected in the peripheral blood of patients with several types of malignancies. However, the role of these cells in anticancer immunity are not yet clear and CD8(+)CD28(neg.) T cells are a controversially discussed subpopulation reported both as immunosuppressive and cytotoxic. In this study, we examined the T cell receptor (TCR) repertoire and complementarity-determining region 3 sequences of CD28(neg.) T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status...
November 14, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#11
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123524/vertebrate-adaptive-immunity-comparative-insights-from-a-teleost-model
#12
REVIEW
Harry W Dickerson, Robert Craig Findly
The channel catfish (Ictalurus punctatus) and the ciliated protozoan parasite Ichthyophthirius multifiliis are used to study pathogen-specific protective immunity. In this review, we briefly describe this host-parasite system and discuss the comparative insights it provides on the adaptive immune response of vertebrates. We include studies related to cutaneous mucosal immunity, B cell memory responses, and analyses of αβ T cell receptor (TCR) repertoires. This host-parasite model has played an important role in elucidating host protective responses to parasite invasion and for comparative studies of vertebrate immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29106696/the-mechanisms-shaping-the-repertoire-of-cd4-foxp3-treg-cells
#13
REVIEW
Piotr Kraj, Leszek Ignatowicz
Regulatory T (Treg ) cells expressing Foxp3 transcription factor control homeostasis of the immune system, antigenic responses to commensal and pathogenic microbiota, and immune responses to self and tumor antigens. Treg cells differentiate in the thymus, (tTreg ) along with conventional CD4(+) T cells, in processes of positive and negative selection. Another class of Treg cells is generated in peripheral tissues (pTreg ) by inducing Foxp3 expression in conventional CD4(+) T cells in response to antigenic stimulation...
November 6, 2017: Immunology
https://www.readbyqxmd.com/read/29103899/perturbation-of-the-t-cell-receptor-repertoire-occurs-with-increasing-age-in-dogs
#14
Angela Holder, Samantha M Mirczuk, Robert C Fowkes, Donald B Palmer, Richard Aspinall, Brian Catchpole
Immunosenescence is the gradual deterioration in immune system function associated with ageing. This decline is partly due to involution of the thymus, which leads to a reduction in the output of naive T cells into the circulating lymphocyte pool. Expansion of existing naive and memory T cell populations, to compensate for the reduction in thymic output, can lead to reduced diversity in the T cell repertoire with increasing age, resulting in impairment of immune responses to novel antigenic challenges, such as during infection and vaccination...
October 28, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29080364/comparative-analysis-of-murine-t-cell-receptor-repertoires
#15
REVIEW
Mark Izraelson, Tatiana O Nakonechnaya, Bruno Moltedo, Evgeniy S Egorov, Sofya A Kasatskaya, Ekaterina V Putintseva, Ilgar Z Mamedov, Dmitriy B Staroverov, Irina I Shemiakina, Maria Y Zakharova, Alexey N Davydov, Dmitriy A Bolotin, Mikhail Shugay, Dmitriy M Chudakov, Alexander Y Rudensky, Olga V Britanova
On the way of understanding the rules and laws of adaptive immunity, high-throughput profiling of TCR repertoires becomes a powerful tool. The structure of TCR repertoires is insightful and instructive even before antigen specificity of each particular receptor becomes available. It embodies information about the thymic and peripheral selection of T cells, about the readiness of an adaptive immunity to withstand new challenges, about the character, the magnitude, and the memory of immune response, and about the etiological and functional proximity of T cell subsets...
October 28, 2017: Immunology
https://www.readbyqxmd.com/read/29075258/quantitative-characterization-of-the-t-cell-receptor-repertoire-of-na%C3%A3-ve-and-memory-subsets-using-an-integrated-experimental-and-computational-pipeline-which-is-robust-economical-and-versatile
#16
Theres Oakes, James M Heather, Katharine Best, Rachel Byng-Maddick, Connor Husovsky, Mazlina Ismail, Kroopa Joshi, Gavin Maxwell, Mahdad Noursadeghi, Natalie Riddell, Tabea Ruehl, Carolin T Turner, Imran Uddin, Benny Chain
The T cell receptor (TCR) repertoire can provide a personalized biomarker for infectious and non-infectious diseases. We describe a protocol for amplifying, sequencing, and analyzing TCRs which is robust, sensitive, and versatile. The key experimental step is ligation of a single-stranded oligonucleotide to the 3' end of the TCR cDNA. This allows amplification of all possible rearrangements using a single set of primers per locus. It also introduces a unique molecular identifier to label each starting cDNA molecule...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29066026/cd4-cd28-kir-cd11a-hi-t-cells-correlate-with-disease-activity-and-are-characterized-by-a-pro-inflammatory-epigenetic-and-transcriptional-profile-in-lupus-patients
#17
Elizabeth Gensterblum, Paul Renauer, Patrick Coit, Faith M Strickland, Nathan C Kilian, Shaylynn Miller, Mikhail Ognenovski, Jonathan D Wren, Pei-Suen Tsou, Emily E Lewis, Kathleen Maksimowicz-McKinnon, W Joseph McCune, Bruce C Richardson, Amr H Sawalha
OBJECTIVE: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus. METHODS: The size of the CD4+CD28+KIR+CD11a(hi) T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11a(hi) T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29054368/an-intermediate-level-of-cd161-expression-defines-a-novel-activated-inflammatory-and-pathogenic-subset-of-cd8-t-cells-involved-in-multiple-sclerosis
#18
Bryan Nicol, Marion Salou, Isabel Vogel, Alexandra Garcia, Emilie Dugast, Jeremy Morille, Stéphanie Kilens, Eric Charpentier, Audrey Donnart, Steven Nedellec, Marylène Jacq-Foucher, Fabienne Le Frère, Sandrine Wiertlewski, Arnaud Bourreille, Sophie Brouard, Laure Michel, Laurent David, Pierre-Antoine Gourraud, Nicolas Degauque, Arnaud B Nicot, Laureline Berthelot, David-Axel Laplaud
Several lines of evidence support a key role for CD8(+) T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8(+) T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date...
October 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29040163/adipose-tissue-is-enriched-for-activated-and-late-differentiated-cd8-t-cells-and-shows-distinct-cd8-receptor-usage-compared-to-blood-in-hiv-infected-persons
#19
John R Koethe, Wyatt McDonnell, Arion Kennedy, Chike O Abana, Mark Pilkinton, Ian Setliff, Ivelin Georgiev, Louise Barnett, Cindy C Hager, Rita Smith, Spyros A Kalams, Alyssa Hasty, Simon Mallal
BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression...
October 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29033130/tumor-and-microenvironment-evolution-during-immunotherapy-with-nivolumab
#20
Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter J Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan
The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy...
November 2, 2017: Cell
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