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https://www.readbyqxmd.com/read/28518056/functionally-diverse-human-t-cells-recognize-non-microbial-antigens-presented-by-mr1
#1
Marco Lepore, Artem Kalinichenko, Salvatore Calogero, Pavanish Kumar, Bhairav Paleja, Mathias Schmaler, Vipin Narang, Francesca Zolezzi, Michael Poidinger, Lucia Mori, Gennaro De Libero
MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28514688/the-e-id-protein-axis-specifies-adaptive-lymphoid-cell-identity-and-suppresses-thymic-innate-lymphoid-cell-development
#2
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/28514665/systems-analysis-reveals-high-genetic-and-antigen-driven-predetermination-of-antibody-repertoires-throughout-b-cell-development
#3
Victor Greiff, Ulrike Menzel, Enkelejda Miho, Cédric Weber, René Riedel, Skylar Cook, Atijeh Valai, Telma Lopes, Andreas Radbruch, Thomas H Winkler, Sai T Reddy
Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen exposure (three structurally different proteins), and (3) four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size) extracted from antibody repertoire sequencing data (400 million reads)...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28512625/using-murine-models-to-investigate-tumor-lymphoid-interactions-spotlight-on-chronic-lymphocytic-leukemia-and-angioimmunoblastic-t-cell-lymphoma
#4
REVIEW
Tyler A Herek, Christine E Cutucache
The role of the tumor microenvironment in leukemias and lymphomas is well established, yet the intricacies of how the malignant cells regulate and influence their non-malignant counterparts remain elusive. For example, chronic lymphocytic leukemia (CLL) is an expansion of malignant CD5(+)CD19(+) B cells, yet the non-malignant T cells play just as large of a role in disease presentation and etiology. Herein, we review the dynamic tumor cell to lymphoid repertoire interactions found in two non-Hodgkin's lymphoma subtypes: CLL and angioimmunoblastic T-cell lymphoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28512452/towards-identifying-protective-b-cell-epitopes-the-pspa-story
#5
REVIEW
Naeem Khan, Arif T Jan
Pneumococcal surface protein A (PspA) is one of the most abundant cell surface protein of Streptococcus pneumoniae (S. pneumoniae). PspA variants are structurally and serologically diverse and help evade complement-mediated phagocytosis of S. pneumoniae, which is essential for its survival in the host. PspA is currently been screened for employment in the generation of more effective (serotype independent) vaccine to overcome the limitations of polysaccharide based vaccines, providing serotype specific immune responses...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28510537/converging-evolution-leads-to-near-maximal-junction-diversity-through-parallel-mechanisms-in-b-and-t-cell-receptors
#6
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/28510446/modularly-constructed-synthetic-granzyme-b-molecule-enables-interrogation-of-intracellular-proteases-for-targeted-cytotoxicity
#7
Patrick Ho, Christopher Ede, Yvonne Y Chen
Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity...
May 16, 2017: ACS Synthetic 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/28500641/t-and-b-cell-clonal-expansion-in-ras-associated-lymphoproliferative-disease-rald-as-revealed-by-next-generation-sequencing
#10
Sarina Levy-Mendelovich, Atar Lev, Erez Rechavi, Ortal Barel, Hana Golan, Bela Bielorai, Yoram Neumann, Amos J Simon, Raz Somech
Ras associated lymphoproliferative disease (RALD) is an autoimmune lymphoproliferative syndrome (ALPS)-like disease caused by mutations in KRAS or NRAS. The immunological phenotype and pathogenesis of RALD have yet to be extensively studied. Here we report a thorough immunological investigation of a RALD patient with a somatic KRAS mutation. Patient lymphocytes were analyzed for phenotype, immunoglobulin levels and T cell proliferation capacity. T and B cell receptor excision circles (TREC and KREC, respectively), markers of naïve T and B cell production, were serially measured over three years...
May 12, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28498152/oligoclonal-t-cell-receptor-repertoire-in-colonic-biopsies-of-patients-with-microscopic-colitis-and-ulcerative-colitis
#11
Sezin Günaltay, Dirk Repsilber, Gisela Helenius, Nils Nyhlin, Johan Bohr, Olof Hultgren, Elisabeth Hultgren Hörnquist
BACKGROUND: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology. METHODS: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCRβ) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with noninflamed colons using next-generation sequencing...
May 10, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28496352/identification-of-expanded-t-cell-clones-by-spectratyping-in-nonfunctioning-kidney-transplants
#12
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/28495875/macrophage-function-in-tissue-repair-and-remodeling-requires-il-4-or-il-13-with-apoptotic-cells
#13
Lidia Bosurgi, Y Grace Cao, Mar Cabeza-Cabrerizo, Andrea Tucci, Lindsey D Hughes, Yong Kong, Jason S Weinstein, Paula Licona-Limon, Edward T Schmid, Facundo Pelorosso, Nicola Gagliani, Joseph E Craft, Richard A Flavell, Sourav Ghosh, Carla V Rothlin
Tissue repair is a subset of a broad repertoire of IL-4/IL-13-dependent host responses during helminth infection. Here, we show that IL-4/IL-13 alone were not sufficient, but IL-4/IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory/tissue repair genes in the lung following helminth infection or in the gut following induction of colitis...
May 11, 2017: Science
https://www.readbyqxmd.com/read/28495553/the-expanding-repertoire-of-targets-for-immune-checkpoint-inhibition-in-bladder-cancer-what-lies-beneath-the-tip-of-the-iceberg-pd-l1
#14
REVIEW
Alexander Sankin, Deepa Narasimhulu, Peter John, Benjamin Gartrell, Mark Schoenberg, Xingxing Zang
Over the last decade, a new understanding of tumor-immune system interplay has been ushered in, lead in large part by the discovery of immune checkpoints mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1 immune checkpoint pathway has already shown great success as a cancer immunotherapy for advanced urothelial carcinoma, leading to durable clinical remissions in an otherwise incurable disease. There are newly described members of the B7-CD28 family including B7-H3, B7x, and HHLA2...
May 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28494274/personalized-t-cell-mediated-cancer-immunotherapy-progress-and-challenges
#15
REVIEW
Michael T Bethune, Alok V Joglekar
Immunotherapies are yielding effective treatments for several previously untreatable cancers. Until recently, vaccines and adoptive cell therapies have been designed to target public tumor antigens common to multiple patients rather than private antigens specific to a single patient. Due to the difficulty of identifying public antigens that are expressed exclusively on tumor cells, these studies have yielded both clinical successes and serious immune-related adverse events. Multiple avenues of research now underscore the centrality of tumor-specific mutated private antigens to endogenous anti-tumor immunity...
May 8, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28493882/selective-pre-priming-of-ha-specific-cd4-t-cells-restores-immunological-reactivity-to-ha-on-heterosubtypic-influenza-infection
#16
Shabnam Alam, Cory Chan, Xing Qiu, Ian Shannon, Chantelle L White, Andrea J Sant, Jennifer L Nayak
A hallmark of the immune response to influenza is repeated encounters with proteins containing both genetically conserved and variable components. Therefore, the B and T cell repertoire is continually being remodeled, with competition between memory and naïve lymphocytes. Our previous work using a mouse model of secondary heterosubtypic influenza infection has shown that this competition results in a focusing of CD4 T cell response specificity towards internal virion proteins with a selective decrease in CD4 T cell reactivity to the novel HA epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28490574/early-emergence-of-cd19-negative-human-antibody-secreting-cells-at-the-plasmablast-to-plasma-cell-transition
#17
Gururaj Arumugakani, Sophie J Stephenson, Darren J Newton, Andy Rawstron, Paul Emery, Gina M Doody, Dennis McGonagle, Reuben M Tooze
Long-lived human plasma cells (PCs) play central roles in immunity and autoimmunity and are enriched among the subpopulation of CD19(neg) human PCs. However, whether human CD19(neg) PCs are necessarily aged cells that have gradually lost CD19 expression is not known. Assessing peripheral blood samples at steady-state and during the acute response to influenza vaccination in healthy donors, we identify the presence of phenotypic CD19(neg) plasmablasts, the proliferative precursor state to mature PCs, and demonstrate by ELISPOT that these are Ab-secreting cells (ASCs)...
May 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28489338/regulatory-t-cells-promote-natural-killer-cell-education-in-mixed-chimeras
#18
Benedikt Mahr, Nina Pilat, Svenja Maschke, Nicolas Granofszky, Christoph Schwarz, Lukas Unger, Karin Hock, Andreas M Farkas, Christoph Klaus, Heinz Regele, Thomas Wekerle
Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in non-irradiated recipient mice conditioned with costimulation blockade and mTOR inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation (BMT) led to BM engraftment and persistent chimerism without Treg transfer, but failed to induce skin graft tolerance...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28481982/mcpas-tcr-a-manually-curated-catalogue-of-pathology-associated-t-cell-receptor-sequences
#19
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/28480300/toward-a-rapid-production-of-multivirus-specific-t-cells-targeting-bkv-adenovirus-cmv-and-ebv-from-umbilical-cord-blood
#20
Hema Dave, Min Luo, J W Blaney, Shabnum Patel, Cecilia Barese, Conrad Russell Cruz, Elizabeth J Shpall, Catherine M Bollard, Patrick J Hanley
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
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