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https://www.readbyqxmd.com/read/28920588/%C3%AE-%C3%AE-t-cells-in-homeostasis-and-host-defence-of-epithelial-barrier-tissues
#1
REVIEW
Morten M Nielsen, Deborah A Witherden, Wendy L Havran
Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance...
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28916722/phosphoproteomics-reveals-that-glycogen-synthase-kinase-3-phosphorylates-multiple-splicing-factors-and-is-associated-with-alternative-splicing
#2
Mansi Y Shinde, Simone Sidoli, Katarzyna Kulej, Michael J Mallory, Caleb M Radens, Amanda Reicherter, Rebecca L Myers, Yoseph Barash, Kristen W Lynch, Benjamin A Garcia, Peter S Klein
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif (pS/pTXXXS/T), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry (MS) techniques to analyze the repertoire of GSK-3-dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ~2...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28902916/targeted-n-glycan-deletion-at-the-receptor-binding-site-retains-hiv-env-nfl-trimer-integrity-and-accelerates-the-elicited-antibody-response
#3
Viktoriya Dubrovskaya, Javier Guenaga, Natalia de Val, Richard Wilson, Yu Feng, Arlette Movsesyan, Gunilla B Karlsson Hedestam, Andrew B Ward, Richard T Wyatt
Extensive shielding by N-glycans on the surface of the HIV envelope glycoproteins (Env) restricts B cell recognition of conserved neutralizing determinants. Elicitation of broadly neutralizing antibodies (bNAbs) in selected HIV-infected individuals reveals that Abs capable of penetrating the glycan shield can be generated by the B cell repertoire. Accordingly, we sought to determine if targeted N-glycan deletion might alter antibody responses to Env. We focused on the conserved CD4 binding site (CD4bs) since this is a known neutralizing determinant that is devoid of glycosylation to allow CD4 receptor engagement, but is ringed by surrounding N-glycans...
September 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28900149/assessment-of-t-cell-receptor-repertoire-and-clonal-expansion-in-peripheral-t-cell-lymphoma-using-rna-seq-data
#4
Qiang Gong, Chao Wang, Weiwei Zhang, Javeed Iqbal, Yang Hu, Timothy C Greiner, Adam Cornish, Jo-Heon Kim, Raul Rabadan, Francesco Abate, Xin Wang, Giorgio G Inghirami, Timothy W McKeithan, Wing C Chan
T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898208/interpreting-the-t-cell-receptor-repertoire
#5
Robert A Holt
No abstract text is available yet for this article.
September 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28898199/a-druggable-secretory-protein-maturase-of-toxoplasma-essential-for-invasion-and-egress
#6
Sunil Kumar Dogga, Budhaditya Mukherjee, Damien Jacot, Tobias Kockmann, Luca Molino, Pierre-Mehdi Hammoudi, Ruben C Hartkoorn, Adrian B Hehl, Dominique Soldati-Favre
Micronemes and rhoptries are specialized secretory organelles that deploy their contents at the apical tip of apicomplexan parasites in a regulated manner. The secretory proteins participate in motility, invasion, and egress and are subjected to proteolytic maturation prior to organellar storage and discharge. Here we establish that Toxoplasma gondii aspartyl protease 3 (ASP3) resides in the endosomal-like compartment and is crucially associated to rhoptry discharge during invasion and to host cell plasma membrane lysis during egress...
September 12, 2017: ELife
https://www.readbyqxmd.com/read/28895901/delayed-activation-kinetics-of-th2-and-th17-cells-compared-to-th1-cells
#7
Andrea Duechting, Anna Przybyla, Stefanie Kuerten, Paul V Lehmann
During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively...
September 12, 2017: Cells
https://www.readbyqxmd.com/read/28891256/composition-and-variation-analysis-of-the-tcr-%C3%AE-chain-cdr3-repertoire-in-neonatal-sepsis
#8
Jinqiao Sun, Bijun Sun, Yanyan Gao, Fusheng He, Lin Yang, Mingbang Wang, Wenhao Zhou
T cell receptor (TCR) diversity is clearly related to protection from infection. However, the characteristics of TCR diversity in neonates are not clear. In this study, we investigated the TCR diversity of neonates with sepsis. Twenty neonates with severe sepsis and 8 matched neonates without infection were enrolled in the study. For the neonates with sepsis, EDTA-anticoagulated blood was collected on day 1 after the diagnosis of sepsis and on day 7 of treatment. For the neonates without infection, blood was collected one time...
September 11, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28888033/modulation-of-%C3%AE-%C3%AE-t-cell-activation-by-neutrophil-elastase
#9
Nadia Yasmín Towstyka, Carolina Maiumi Shiromizu, Irene Keitelman, Florencia Sabbione, Gabriela Verónica Salamone, Jorge Raúl Geffner, Analía Silvina Trevani, Carolina Cristina Jancic
γδ T cells are non-conventional, innate-like T cells, characterized by a restricted TCR repertoire. They participate in protective immunity response against extracellular and intracellular pathogens, tumor surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance, and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood γδ T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of IFN-γ and TNF-α induced by anti-CD3 antibodies were potentiated by neutrophils...
September 9, 2017: Immunology
https://www.readbyqxmd.com/read/28886197/in-vivo-lineage-tracing-reveals-axin2-expressing-long-lived-cortical-thymic-epithelial-progenitors-in-the-postnatal-thymus
#10
Si Hui Tan, Roel Nusse
In the thymus, cortical and medullary thymic epithelial cells (TECs) are instrumental for generating a repertoire of functional T cells. Hence, there has been much interest in the ontogeny of TECs. While medullary TEC (mTEC) and bipotent progenitors have been identified, the existence of a cortical TEC (cTEC) progenitor remains ambiguous. In this study, we used lineage tracing based on a target gene of the Wnt pathway, Axin2. We found that Axin2 initially labels cells in both the cortical and medullary compartments...
2017: PloS One
https://www.readbyqxmd.com/read/28878738/overlooked-mechanisms-in-type-1-diabetes-etiology-how-unique-costimulatory-molecules-contribute-to-diabetogenesis
#11
REVIEW
David H Wagner
Type 1 Diabetes (T1D) develops when immune cells invade the pancreatic islets resulting in loss of insulin production in beta cells. T cells have been proven to be central players in that process. What is surprising, however, is that classic mechanisms of tolerance cannot explain diabetogenesis; alternate mechanisms must now be considered. T cell receptor (TCR) revision is the process whereby T cells in the periphery alter TCR expression, outside the safety-net of thymic selection pressures. This process results in an expanded T cell repertoire, capable of responding to a universe of pathogens, but limitations are that increased risk for autoimmune disease development occurs...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28878121/a-tcr%C3%AE-framework-centered-codon-shapes-a-biased-t-cell-repertoire-through-direct-mhc-and-cdr3%C3%AE-interactions
#12
Kristin Støen Gunnarsen, Lene Støkken Høydahl, Louise Fremgaard Risnes, Shiva Dahal-Koirala, Ralf Stefan Neumann, Elin Bergseng, Terje Frigstad, Rahel Frick, M Fleur du Pré, Bjørn Dalhus, Knut Ea Lundin, Shuo-Wang Qiao, Ludvig M Sollid, Inger Sandlie, Geir Åge Løset
Selection of biased T cell receptor (TCR) repertoires across individuals is seen in both infectious diseases and autoimmunity, but the underlying molecular basis leading to these shared repertoires remains unclear. Celiac disease (CD) occurs primarily in HLA-DQ2.5+ individuals and is characterized by a CD4+ T cell response against gluten epitopes dominated by DQ2.5-glia-α1a and DQ2.5-glia-α2. The DQ2.5-glia-α2 response recruits a highly biased TCR repertoire composed of TRAV26-1 paired with TRBV7-2 harboring a semipublic CDR3β loop...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28878083/how-germinal-centers-evolve-broadly-neutralizing-antibodies-the-breadth-of-the-follicular-helper-t-cell-response
#13
Rob J De Boer, Alan S Perelson
Many HIV-1 infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years, and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest affinity receptors tend to acquire the most antigen from the FDC network, and present the highest density of cognate peptides to follicular helper T cells (Tfh), which provide survival signals to the B cell. BnAbs are therefore only expected to evolve when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than other lineages of more specific B cells...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28878078/potent-plasmablast-derived-antibodies-elicited-by-the-nih-dengue-vaccine
#14
Diogo M Magnani, Cassia G T Silveira, Michael J Ricciardi, Lucas Gonzalez-Nieto, Núria Pedreño-Lopez, Varian K Bailey, Martin J Gutman, Helen S Maxwell, Aline Domingues, Priscilla R Costa, Lilian Ferrari, Raphaella Goulart, Mauricio A Martins, José M Martinez-Navio, Sebastian P Fuchs, Jorge Kalil, Maria do Carmo Timenetsky, Jens Wrammert, Stephen S Whitehead, Dennis R Burton, Ronald C Desrosiers, Esper G Kallas, David I Waktins
Exposure to dengue virus (DENV) is thought to elicit lifelong immunity, mediated by DENV-neutralizing antibodies (nAbs). However, Abs generated by primary infections confer serotype-specific protection, and immunity against other serotypes only develops after subsequent infections. Accordingly, the induction of these nAb responses acquired after serial DENV infections has been a long sought-after goal for vaccination. Nonetheless, it is still unclear if tetravalent vaccines can elicit or recall nAbs. Here, we have characterized the responses from a volunteer who had been previously exposed to DENV and was immunized with the live attenuated tetravalent vaccine Butantan-DV, developed by the NIH and Butantan...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28874533/type-1-diabetes-induction-in-humanized-mice
#15
Shulian Tan, Yang Li, Jinxing Xia, Chun-Hui Jin, Zheng Hu, Gaby Duinkerken, Yuying Li, Mohsen Khosravi Maharlooei, Estefania Chavez, Grace Nauman, Nichole Danzl, Maki Nakayama, Bart O Roep, Megan Sykes, Yong-Guang Yang
There is an urgent and unmet need for humanized in vivo models of type 1 diabetes to study immunopathogenesis and immunotherapy, and in particular antigen-specific therapy. Transfer of patient blood lymphocytes to immunodeficient mice is associated with xenogeneic graft-versus-host reactivity that complicates assessment of autoimmunity. Improved models could identify which human T cells initiate and participate in beta-cell destruction and help define critical target islet autoantigens. We used humanized mice (hu-mice) containing robust human immune repertoires lacking xenogeneic graft-versus-host reactivity to address this question...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28871256/human-leukocyte-antigen-hla-drb1-15-01-and-hla-drb5-01-01-present-complementary-peptide-repertoires
#16
Erika Margaret Scholz, Miguel Marcilla, Xavier Daura, David Arribas-Layton, Eddie A James, Iñaki Alvarez
Human leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding assays. DR2a could display a set of peptides complementary to that presented by DR2b or, alternatively, a similar peptide repertoire but recognized in a different manner by T cells. It is known that DR2a and DR2b share some peptide ligands, although the degree of similarity of their associated peptidomes remains unclear...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28868054/therapeutic-antibodies-against-intracellular-tumor-antigens
#17
REVIEW
Iva Trenevska, Demin Li, Alison H Banham
Monoclonal antibodies are among the most clinically effective drugs used to treat cancer. However, their target repertoire is limited as there are relatively few tumor-specific or tumor-associated cell surface or soluble antigens. Intracellular molecules represent nearly half of the human proteome and provide an untapped reservoir of potential therapeutic targets. Antibodies have been developed to target externalized antigens, have also been engineered to enter into cells or may be expressed intracellularly with the aim of binding intracellular antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28866803/personalized-ex-vivo-multiple-peptide%C3%A2-enrichment-and-detection-of-t-cells-reactive-to-multiple-tumor-associated-antigens-in-prostate-cancer-patients
#18
Pavla Taborska, Dmitry Stakheev, Zuzana Strizova, Katerina Vavrova, Michal Podrazil, Jirina Bartunkova, Daniel Smrz
Personalized peptide vaccination is a promising immunotherapeutic approach in prostate cancer (PCa). We therefore examined whether an approach, utilizing personalized multiple peptide-mediated ex vivo enrichment with effector T cells reactive to multiple tumor-associated antigens (TAAs), could be employed as a basis for the development of T cell immunotherapy of PCa. In this study, we used the non-adherent fraction (lymphocytes) of cryopreserved peripheral blood mononuclear cells from a leukapheretic product of biochemically recurrent (BR, n = 14) and metastatic hormone-refractory (HR, n = 12) PCa patients...
September 2, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28866385/t-cell-receptor-sequencing-reveals-decreased-diversity-18-years-after-early-thymectomy
#19
Judith Gudmundsdottir, Christina Lundqvist, Hanna IJspeert, Eva van der Slik, Sólveig Óskarsdóttir, Susanne Lindgren, Vanja Lundberg, Martin Berglund, Jenny Lingman-Framme, Esbjörn Telemo, Mirjam van der Burg, Olov Ekwall
Next generation T and B cell receptor sequencing in individuals 18 years after early thymectomy (n=11) due to congenital cardiac malformation reveals decreased diversity in both helper and cytotoxic T cell receptor repertoires whereas the B cell repertoire remains unaffected.
August 30, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28865188/phenograph-and-visne-facilitate-the-identification-of-abnormal-t-cell-populations-in-routine-clinical-flow-cytometric-data
#20
Joseph A DiGiuseppe, Jolene L Cardinali, William N Rezuke, Dana Pe'er
BACKGROUND: Flow cytometric identification of neoplastic T-cell populations is complicated by the wide range of phenotypic abnormalities in T-cell neoplasia, and the diverse repertoire of reactive T-cell phenotypes. We evaluated whether a recently described clustering algorithm, PhenoGraph, and dimensionality-reduction algorithm, viSNE, might facilitate the identification of abnormal T-cell populations in routine clinical flow cytometric data. METHODS: We applied PhenoGraph and viSNE to peripheral blood mononuclear cells labeled with a single 8-color T/NK-cell antibody combination...
September 2, 2017: Cytometry. Part B, Clinical Cytometry
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