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TCR signaling

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https://www.readbyqxmd.com/read/27922818/age-related-changes-in-the-gene-expression-profile-of-antigen-specific-mouse-cd8-t-cells-can-be-partially-reversed-by-blockade-of-the-btla-cd160-pathways-during-vaccination
#1
Noor Dawany, Elizabeth M Parzych, Louise C Showe, Hildegund Cj Ertl
We analyzed gene expression profiles of young and aged mouse CD8(+) T cells specific for the nucleoprotein (NP) of influenza A/PR8/34 virus. CD8(+) T cells were stimulated either by the NP antigen expressed in its native form or fused into the herpes virus (HSV)-1 glycoprotein D (gD) protein, which blocks signaling through the immunoinhibitory B and T lymphocyte attenuator (BTLA) and CD160 pathways. We show that NP-specific CD8(+) T cells from aged mice exhibit numerous differences in gene expression compared to NP-specific CD8(+) T cells from young mice, including a significant reduction of expression in genes involved in T cell receptor (TcR) and CD28 signaling...
November 9, 2016: Aging
https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#2
REVIEW
Si-Fa Gao, Bo Zhong, Dandan Lin
CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27910998/aurora-a-shines-on-t-cell-activation-through-the-regulation-of-lck
#3
Noelia Blas-Rus, Eugenio Bustos-Morán, Noa B Martín-Cófreces, Francisco Sánchez-Madrid
Different protein kinases control signaling emanating from the T cell receptor (TCR) during antigen-specific T cell activation. Mitotic kinases, e.g. Aurora-A, have been widely studied in the context of mitosis due to their role during microtubule (MT) nucleation, becoming critical regulators of cell cycle progression. We have recently described a specific role for Aurora-A kinase in antigenic T cell activation. Blockade of Aurora-A in T cells severely disrupts the dynamics of MTs and CD3ζ-bearing signaling vesicles during T cell activation...
December 2, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27903736/t-and-b-cell-markers-in-dried-blood-spots-of-neonates-with-congenital-cytomegalovirus-infection-b-cell-numbers-at-birth-are-associated-with-long-term-outcomes
#4
Roberta Rovito, Marjolein J Korndewal, Menno C van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C M Kroes, Anton W Langerak, Ann C T M Vossen
Congenital CMV infection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecular markers of T and B cell numbers in neonatal dried blood spots of 99 children with cCMV and 54 children without cCMV: δRec-ψJα signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igκ-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vδ1-Jδ1, and Vδ2-Jδ1 rearrangements...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27900794/fast-and-efficient-free-induction-decay-mr-spectroscopic-imaging-of-the-human-brain-at-9-4-tesla
#5
Grzegorz L Chadzynski, Jonas Bause, Gunamony Shajan, Rolf Pohmann, Klaus Scheffler, Philipp Ehses
PURPOSE: The purpose of this work was to develop a fast and efficient MRSI-FID acquisition scheme and test its performance in vivo. The aim was to find a trade-off between the minimal total acquisition time and signal-to-noise ratio of the acquired spectra. METHODS: Measurements were performed on a 9.4 Tesla system. Sequence optimization included redesign of water suppression, optimization of the sequence gradients, and improvement of the sampling efficiency by minimizing the read-out time...
November 29, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#6
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899444/antigen-dependent-competition-shapes-the-local-repertoire-of-tissue-resident-memory-cd8-t-cells
#7
Andreas Muschaweckh, Veit R Buchholz, Anne Fellenzer, Christian Hessel, Paul-Albert König, Sha Tao, Ronny Tao, Mathias Heikenwälder, Dirk H Busch, Thomas Korn, Wolfgang Kastenmüller, Ingo Drexler, Georg Gasteiger
Tissue-resident memory CD8(+) T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#8
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27893767/t-cells-of-infants-are-mature-but-hyporeactive-due-to-limited-ca2-influx
#9
Kristin Schmiedeberg, Hardy Krause, Friedrich-Wilhelm Röhl, Roland Hartig, Gerhard Jorch, Monika C Brunner-Weinzierl
CD4 T cells in human infants and adults differ in the initiation and strength of their responses. The molecular basis for these differences is not yet understood. To address this the principle key molecular events of TCR- and CD28-induced signaling in naive CD4 T cells, such as Ca2+ influx, NFAT expression, phosphorylation and translocation into the nucleus, ERK activation and IL-2 response, were analyzed over at least the first 3 years of life. We report dramatically reduced IL-2 and TNFα responses in naive CD31+ T cells during infancy...
2016: PloS One
https://www.readbyqxmd.com/read/27891502/diacylglycerol-kinases-in-t-cell-tolerance-and-effector-function
#10
REVIEW
Shelley S Chen, Zhiming Hu, Xiao-Ping Zhong
Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR) signal by recruiting multiple effector molecules, such as RasGRP1, PKCθ, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms, α and ζ, in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27891224/tcr-signaling-by-conventional-cd4-t-cells-is-required-for-optimal-maintenance-of-peripheral-regulatory-t-cell-numbers
#11
Theresa M Leichner, Atsushi Satake, Taku Kambayashi
To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely indexed to the number of conventional T cells (Tconvs) so that an adequate Treg:Tconv ratio can be maintained. Two factors important in this process are the cytokine interleukin-2 (IL-2) and T cell receptor (TCR) stimulation by major histocompatibility complex class II (MHC-II). Here, we report that in addition to TCR stimulation of Tregs themselves, the maintenance of Tregs also requires TCR signaling by Tconvs. We found that Tconvs produce IL-2 in response to self-peptide-MHC-II complexes and that Tconvs possessing more highly self-reactive TCRs express more IL-2 at baseline...
June 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27883938/pretreatment-of-activated-human-cd8-t-cells-with-il-12-leads-to-enhanced-tcr-induced-signaling-and-cytokine-production
#12
Aldo Vacaflores, Samantha N Freedman, Nicole M Chapman, Jon C D Houtman
During the immune response to pathogens and autoantigens, CD8T cells are exposed to numerous inflammatory agents including the cytokine IL-12. Previous studies have focused on how IL-12 regulates T cell functions when present during or after the activation of the T cell receptor (TCR). However, recent studies suggest that prior exposure to IL-12 also alters the TCR responsiveness of murine T cells. Whether similar phenomena occur in human activated CD8T cells and the mechanisms mediating these effects remain unexplored...
November 21, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27881740/peripheral-self-reactivity-regulates-antigen-specific-cd8-t-cell-responses-and-cell-division-under-physiological-conditions
#13
Lee Kim Swee, Zhen Wei Tan, Anna Sanecka, Nagisa Yoshida, Harshil Patel, Gijsbert Grotenbreg, Eva-Maria Frickel, Hidde L Ploegh
T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity-hence reactivity to self-and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2(b) haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 L(d)-restricted epitope, derived from the Rop7 protein of Toxoplasma gondii We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27875277/development-of-nanoscale-structure-in-lat-based-signaling-complexes
#14
Valarie A Barr, Eilon Sherman, Jason Yi, Itoro Akpan, Alexandre K Rouquette-Jazdanian, Lawrence E Samelson
The adapter molecule Linker for Activation of T cells (LAT) plays a critical role in forming signaling complexes induced by stimulation of the T cell receptor (TCR). These multi-molecular complexes are dynamic structures that activate highly regulated signaling pathways. Previously, we demonstrated nanoscale structure in LAT-based complexes where the adapter SLP-76 localizes to the periphery of LAT clusters. In this study, we show that initially LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR engagement...
November 10, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27869819/a-cycle-of-zap70-kinase-activation-and-release-from-the-tcr-amplifies-and-disperses-antigenic-stimuli
#15
Zachary B Katz, Lucie Novotná, Amy Blount, Björn F Lillemeier
Cell-surface-receptor pathways amplify weak, rare and local stimuli to induce cellular responses. This task is accomplished despite signaling components that segregate into nanometer-scale membrane domains. Here we describe a 'catch-and-release' mechanism that amplified and dispersed stimuli by releasing activated kinases from receptors lacking intrinsic catalytic activity. Specifically, we discovered a cycle of recruitment, activation and release for Zap70 kinases at phosphorylated T cell antigen receptors (TCRs)...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27853459/immunosenescence-related-transcriptomic-and-immunologic-changes-in-older-individuals-following-influenza-vaccination
#16
Richard B Kennedy, Inna G Ovsyannikova, Iana H Haralambieva, Ann L Oberg, Michael T Zimmermann, Diane E Grill, Gregory A Poland
The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27852740/temporal-expression-of-bim-limits-the-development-of-agonist-selected-thymocytes-and-skews-their-tcr%C3%AE-repertoire
#17
Kun-Po Li, Anke Fähnrich, Eron Roy, Carla M Cuda, H Leighton Grimes, Harris R Perlman, Kathrin Kalies, David A Hildeman
CD8αα TCRαβ(+) intestinal intraepithelial lymphocytes play a critical role in promoting intestinal homeostasis, although mechanisms controlling their development and peripheral homeostasis remain unclear. In this study, we examined the spatiotemporal role of Bim in the thymic selection of CD8αα precursors and the fate of these cells in the periphery. We found that T cell-specific expression of Bim during early/cortical, but not late/medullary, thymic development controls the agonist selection of CD8αα precursors and limits their private TCRβ repertoire...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27851975/cd8-t-cells-from-human-neonates-are-biased-toward-an-innate-immune-response
#18
Ariel O Galindo-Albarrán, Oscar H López-Portales, Darely Y Gutiérrez-Reyna, Otoniel Rodríguez-Jorge, José Antonio Sánchez-Villanueva, Oscar Ramírez-Pliego, Aurélie Bergon, Béatrice Loriod, Hélène Holota, Jean Imbert, Armando Hernández-Mendoza, Pierre Ferrier, Enrique Carrillo-de Santa Pau, Alfonso Valencia, Salvatore Spicuglia, M Angélica Santana
To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8(+) T cells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in T cell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8(+) T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27833610/tcr-triggering-induces-the-formation-of-lck-rack1-actinin-1-multiprotein-network-affecting-lck-redistribution
#19
Ondřej Ballek, Jan Valečka, Martina Dobešová, Adéla Broučková, Jasper Manning, Pavel Řehulka, Jiří Stulík, Dominik Filipp
The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases, Lck. Upon T-cell antigen receptor (TCR) triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal rearrangement. In addition, the delivery of Lck function requires rapid and targeted membrane redistribution, but the mechanism underpinning this process is largely unknown. To gain insight into this process, we considered previously described proteins that could assist in this process via their capacity to interact with kinases and regulate their intracellular translocations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27823582/domain-swapped-t-cell-receptors-improve-the-safety-of-tcr-gene-therapy
#20
Michael T Bethune, Marvin H Gee, Mario Bunse, Mark S Lee, Eric H Gschweng, Meghana S Pagadala, Jing Zhou, Donghui Cheng, James R Heath, Donald B Kohn, Michael S Kuhns, Wolfgang Uckert, David Baltimore
T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses...
November 8, 2016: ELife
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