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https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#1
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28801931/immunomodulatory-effects-of-adipose-stromal-vascular-fraction-cells-promote-alternative-activation-macrophages-to-repair-tissue-damage
#2
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Isabella Febbo, Bruce A Bunnell
The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are a functional dichotomy that are persuaded according to the surrounding milieu. In both multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this pro-inflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...
August 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28800929/directing-t-cell-fate-how-thymic-antigen-presenting-cells-coordinate-thymocyte-selection
#3
REVIEW
Elise R Breed, S Thera Lee, Kristin A Hogquist
The development of a self-tolerant and effective T cell receptor repertoire is dependent on interactions coordinated by various antigen presenting cells (APC) within the thymus. T cell receptor-self-peptide-MHC interactions are essential for determining T cell fate, however different cytokine and co-stimulatory signals provided by the diverse APCs within the thymus are also critical. Here, we outline the different localization and functional capabilities of thymic APCs. We also discuss how these distinct APCs work collectively to facilitate the establishment of a diverse T cell receptor repertoire that is tolerant to an array of different self-antigens...
August 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28798410/a-novel-signature-for-stratifying-the-molecular-heterogeneity-of-the-tissue-infiltrating-t-cell-receptor-repertoire-reflects-gastric-cancer-prognosis
#4
Manchao Kuang, Jieyao Cheng, Chengli Zhang, Lin Feng, Xue Xu, Yajing Zhang, Ming Zu, Jianfang Cui, Hang Yu, Kaitai Zhang, Aiming Yang, Shujun Cheng
Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794018/redefining-memory-building-the-case-for-adaptive-nk-cells
#5
Silke Paust, Catherine A Blish, R Keith Reeves
Classically, natural killer (NK) cells have been defined by nonspecific innate killing of virus-infected and tumor cells. However, burgeoning evidence suggests that the functional repertoire of NK cells is far more diverse than has been previously appreciated, thus raising the possibility that there could be unexpected functional specialization and even adaptive capabilities among NK cell subpopulations. Some of the first evidence that NK cells respond in an antigen-specific fashion came from experiments revealing that subpopulations of murine NK cells could respond to a specific MCMV protein, and that in the absence of T and B cells, murine NK cells also mediated adaptive immune responses to a secondary challenge with specific haptens...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28783708/preferential-induction-of-cross-group-influenza-a-hemagglutinin-stem-specific-memory-b-cells-after-h7n9-immunization-in-humans
#6
Sarah F Andrews, M Gordon Joyce, Michael J Chambers, Rebecca A Gillespie, Masaru Kanekiyo, Kwanyee Leung, Eun Sung Yang, Yaroslav Tsybovsky, Adam K Wheatley, Michelle C Crank, Jeffrey C Boyington, Madhu S Prabhakaran, Sandeep R Narpala, Xuejun Chen, Robert T Bailer, Grace Chen, Emily Coates, Peter D Kwong, Richard A Koup, John R Mascola, Barney S Graham, Julie E Ledgerwood, Adrian B McDermott
Antigenic drift and shift of influenza strains underscore the need for broadly protective influenza vaccines. One strategy is to design immunogens that elicit B cell responses against conserved epitopes on the hemagglutinin (HA) stem. To better understand the elicitation of HA stem-targeted B cells to group 1 and group 2 influenza subtypes, we compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Upon H7N9 vaccination, almost half of the HA stem-specific response recognized the group 1 and group 2 subtypes, whereas the response to H5N1 was largely group 1-specific...
July 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783691/characterization-of-t-and-b-cell-repertoire-diversity-in-patients-with-rag-deficiency
#7
Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H Bleesing, David Buchbinder, Manish J Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem A Elfeky, Andrea Finocchi, Ramsay L Fuleihan, Andrew R Gennery, Dalia H El-Ghoneimy, Lauren A Henderson, Waleed Al-Herz, Elham Hossny, Robert P Nelson, Sung-Yun Pai, Niraj C Patel, Shereen M Reda, Pere Soler-Palacin, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolan E Walter, Luigi D Notarangelo
Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4)...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28783686/the-checkpoint-for-agonist-selection-precedes-conventional-selection-in-human-thymus
#8
Greet Verstichel, David Vermijlen, Liesbet Martens, Glenn Goetgeluk, Margreet Brouwer, Nicolas Thiault, Yasmine Van Caeneghem, Stijn De Munter, Karin Weening, Sarah Bonte, Georges Leclercq, Tom Taghon, Tessa Kerre, Yvan Saeys, Jo Van Dorpe, Hilde Cheroutre, Bart Vandekerckhove
The thymus plays a central role in self-tolerance, partly by eliminating precursors with a T cell receptor (TCR) that binds strongly to self-antigens. However, the generation of self-agonist-selected lineages also relies on strong TCR signaling. How thymocytes discriminate between these opposite outcomes remains elusive. Here, we identified a human agonist-selected PD-1(+) CD8αα(+) subset of mature CD8αβ(+) T cells that displays an effector phenotype associated with agonist selection. TCR stimulation of immature post-β-selection thymocyte blasts specifically gives rise to this innate subset and fixes early T cell receptor alpha variable (TRAV) and T cell receptor alpha joining (TRAJ) rearrangements in the TCR repertoire...
February 24, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783658/human-thymoproteasome-variations-influence-cd8-t-cell-selection
#9
Takeshi Nitta, Yuta Kochi, Ryunosuke Muro, Yoshihiko Tomofuji, Tadashi Okamura, Shigeo Murata, Harumi Suzuki, Takayuki Sumida, Kazuhiko Yamamoto, Hiroshi Takayanagi
The proteasome is a multi-subunit protease complex essential for housekeeping protein degradation and the production of the major histocompatibility complex (MHC) class I-bound antigen peptides that are essential for recognition by CD8 T cells. MHC variations dramatically contribute to T cell selection and autoimmunity, but genetic variations of peptide processing machinery including proteasome genes have been poorly explored in this context. In the computational analysis of human proteasome gene variation, we documented that PSMB11 was highly enriched for nucleotide changes that interfere with protein function...
June 2, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783656/resident-memory-cd8-t-cells-in-the-upper-respiratory-tract-prevent-pulmonary-influenza-virus-infection
#10
Angela Pizzolla, Thi H O Nguyen, Jeffrey M Smith, Andrew G Brooks, Katherine Kedzieska, William R Heath, Patrick C Reading, Linda M Wakim
Nasal epithelial tissue of the upper respiratory tract is the first site of contact by inhaled pathogens such as influenza virus. We show that this region is key to limiting viral spread to the lower respiratory tract and associated disease pathology. Immunization of the upper respiratory tract leads to the formation of local tissue-resident memory CD8(+) T cells (Trm cells). Unlike Trm cells in the lung, these cells develop independently of local cognate antigen recognition and transforming growth factor-β signaling and persist with minimal decay, representing a long-term protective population...
June 2, 2017: Science Immunology
https://www.readbyqxmd.com/read/28782752/peripheral-clonal-selection-shapes-the-human-%C3%AE-%C3%AE-t-cell-repertoire
#11
Biagio Di Lorenzo, Julie Déchanet-Merville, Bruno Silva-Santos
No abstract text is available yet for this article.
August 7, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28782508/circulating-and-tissue-resident-cd4-t-cells-with-reactivity-to-intestinal-microbiota-are-abundant-in-healthy-individuals-and-function-is-altered-during-inflammation
#12
Ahmed N Hegazy, Nathaniel R West, Michael J T Stubbington, Emily Wendt, Kim I M Suijker, Angeliki Datsi, Sebastien This, Camille Danne, Suzanne Campion, Sylvia H Duncan, Benjamin M J Owens, Holm H Uhlig, Andrew McMichael, Andreas Bergthaler, Sarah A Teichmann, Satish Keshav, Fiona Powrie
BACKGROUND & AIMS: Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4(+) T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation...
August 3, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28780374/maternal-t-and-b-cell-engraftment-in-two-cases-of-x-linked-severe-combined-immunodeficiency-with-igg1-gammopathy
#13
Tsubasa Okano, Takuro Nishikawa, Eri Watanabe, Takashi Watanabe, Takehiro Takashima, Tzu-Wen Yeh, Motoi Yamashita, Mari Tanaka-Kubota, Satoshi Miyamoto, Noriko Mitsuiki, Masatoshi Takagi, Yoshifumi Kawano, Yoshiki Mochizuki, Kohsuke Imai, Hirokazu Kanegane, Tomohiro Morio
X-linked severe combined immunodeficiency (X-SCID), caused by defects in the common gamma chain, is typically characterized by T and NK cell defects with the presence of B cells. T cell dysfunction and impaired class-switch recombination of B cells mean that patients typically have defects in class-switched immunoglobulins (IgG, IgA, and IgE) with detectable IgM. Here, we describe two patients with X-SCID with IgG1 gammopathy, in whom we identified maternal T and B cell engraftment. Exclusively, maternal B cells were found among the IgD(-)CD27(+) class-switched memory B cells, whereas the patients' B cells remained naïve...
August 2, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28775213/lactobacillus-reuteri-induces-gut-intraepithelial-cd4-cd8%C3%AE-%C3%AE-t-cells
#14
Luisa Cervantes-Barragan, Jiani N Chai, Ma Diarey Tianero, Blanda DiLuccia, Philip P Ahern, Joseph Merriman, Victor S Cortez, Michael G Caparon, Mohamed S Donia, Susan Gilfillan, Marina Cella, Jeffrey I Gordon, Chyi-Song Hsieh, Marco Colonna
The small intestine contains CD4(+)CD8αα(+) double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4(+) T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28774790/recovery-and-assessment-of-leukocytes-from-lr-express-filters
#15
Abby K Wegehaupt, Ellen K Roufs, Cory R Hewitt, Marisela L Killian, Oxana Gorbatenko, Cynthia M Anderson, M Scott Killian
Leukocytes, or white blood cells, are used for a variety of investigational purposes and they offer advantages over laboratory-adapted cell lines. Leukocytes that are typically discarded by blood banks during the collection of red blood cells, platelets, and plasma can often be obtained for research use. However, the available leukocytes are frequently contained within a blood filtration device, such as the Terumo LR Express (TLRE) filter. In this study, procedures were evaluated for the ability to elute viable leukocytes from TLRE filters...
July 31, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28771750/comprehensive-t-cell-immunophenotyping-and-next-generation-sequencing-from-hpv-positive-and-negative-head-and-neck-squamous-cell-carcinomas
#16
Kate Poropatich, Joel Fontanarosa, Suchitra Swaminathan, Dave Dittmann, Siqi Chen, Sandeep Samant, Bin Zhang
The success of PD-1 inhibition in achieving a clinical response in a subset of HNSCC patients emphasizes the need to better understand the immunobiology of head and neck squamous cell carcinomas (HNSCC). Immunophenotyping was performed on 30 patients with HNSCC (16 HPV-positive, 14 HPV-negative) from matched tissue from the primary tumor site, locally metastatic cervical lymph nodes (LN), uninvolved local cervical LN and peripheral blood. CD4(+) and CD8(+) T cell lymphocytes obtained from tissue were analyzed for expression levels of inhibitory receptors PD-1, TIM-3 and CTLA-4...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28771103/overcoming-barriers-of-car-t-cell-therapy-in-patients-with-mesothelin-expressing-cancers
#17
Mark H O'Hara, Caitlin Stashwick, Gabriela Plesa, Janos L Tanyi
One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28770318/regulatory-t-cell-dysfunction-in-type-1-diabetes-what-s-broken-and-how-can-we-fix-it
#18
REVIEW
Caroline M Hull, Mark Peakman, Timothy I M Tree
Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4(+) and CD8(+) T cells with specificity for islet autoantigens...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28768912/single-cell-profiling-reveals-gpcr-heterogeneity-and-functional-patterning-during-neuroinflammation
#19
Denise Tischner, Myriam Grimm, Harmandeep Kaur, Daniel Staudenraus, Jorge Carvalho, Mario Looso, Stefan Günther, Florian Wanke, Sonja Moos, Nelly Siller, Johanna Breuer, Nicholas Schwab, Frauke Zipp, Ari Waisman, Florian C Kurschus, Stefan Offermanns, Nina Wettschureck
GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells, macrophages, microglia, or endothelial cells...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28768193/immunogenetic-profiling-for-gastric-cancers-identifies-sulfated-glycosaminoglycans-as-major-and-functional-b-cell-antigens-in-human-malignancies
#20
Hiroto Katoh, Daisuke Komura, Hiroki Konishi, Ryohei Suzuki, Asami Yamamoto, Miwako Kakiuchi, Reiko Sato, Tetsuo Ushiku, Shogo Yamamoto, Kenji Tatsuno, Takashi Oshima, Sachiyo Nomura, Yasuyuki Seto, Masashi Fukayama, Hiroyuki Aburatani, Shumpei Ishikawa
Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires...
August 1, 2017: Cell Reports
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