scholarly journals miR-146a controls the resolution of T cell responses in mice

2012 ◽  
Vol 209 (9) ◽  
pp. 1655-1670 ◽  
Author(s):  
Lili Yang ◽  
Mark P. Boldin ◽  
Yang Yu ◽  
Claret Siyuan Liu ◽  
Chee-Kwee Ea ◽  
...  
Keyword(s):  
T Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Inflammatory Diseases ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Immune Protection ◽  
Tcr Signaling ◽  
Cell Responses ◽  
Negative Feedback Control

T cell responses in mammals must be tightly regulated to both provide effective immune protection and avoid inflammation-induced pathology. NF-κB activation is a key signaling event induced by T cell receptor (TCR) stimulation. Dysregulation of NF-κB is associated with T cell–mediated inflammatory diseases and malignancies, highlighting the importance of negative feedback control of TCR-induced NF-κB activity. In this study we show that in mice, T cells lacking miR-146a are hyperactive in both acute antigenic responses and chronic inflammatory autoimmune responses. TCR-driven NF-κB activation up-regulates the expression of miR-146a, which in turn down-regulates NF-κB activity, at least partly through repressing the NF-κB signaling transducers TRAF6 and IRAK1. Thus, our results identify miR-146a as an important new member of the negative feedback loop that controls TCR signaling to NF-κB. Our findings also add microRNA to the list of regulators that control the resolution of T cell responses.

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

scholarly journals A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentina Ceglia ◽  
Erin J. Kelley ◽  
Annalee S. Boyle ◽  
Sandra Zurawski ◽  
Heather L. Mead ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Protein Antigens ◽  
Cell Responses ◽  
Tcr Repertoire ◽  
Receptor Clusters ◽  
Theoretical Sensitivity

Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous ‘Clusters of Expanded TCRs (CETs)’ can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones. We show that clonotypes within each CET respond to the same epitope, and that protein antigens stimulate multiple CETs reactive to constituent peptides. Finally, we demonstrate the personalized assignment of antigen-specificity to rare clones within fully-diverse uncultured repertoires. The method presented here may be used to monitor T cell responses to vaccination and immunotherapy with high fidelity.

scholarly journals The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+Oscillations

2003 ◽  
Vol 278 (21) ◽  
pp. 18877-18883 ◽  
Author(s):  
Anders Bergqvist ◽  
Sara Sundström ◽  
Lina Y. Dimberg ◽  
Erik Gylfe ◽  
Maria G. Masucci
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Receptor ◽  
Core Protein ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Cell Responses ◽  
Virus Core

scholarly journals CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

2017 ◽  
Vol 114 (51) ◽  
pp. E10956-E10964 ◽  
Author(s):  
Andrew Chancellor ◽  
Anna S. Tocheva ◽  
Chris Cave-Ayland ◽  
Liku Tezera ◽  
Andrew White ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Head Group ◽  
Computational Simulations ◽  
Functional Responses ◽  
Cell Responses ◽  
Group Movement

Tuberculosis (TB), caused byMycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells.

scholarly journals ILC regulation of T cell responses in inflammatory diseases and cancer

2019 ◽  
Vol 41 ◽  
pp. 101284 ◽  
Author(s):  
Kathrin Warner ◽  
Pamela S. Ohashi
Keyword(s):  
T Cell ◽  
Inflammatory Diseases ◽  
T Cell Responses ◽  
Cell Responses

scholarly journals Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses

2011 ◽  
Vol 108 (23) ◽  
pp. 9536-9541 ◽  
Author(s):  
E. B. Day ◽  
C. Guillonneau ◽  
S. Gras ◽  
N. L. La Gruta ◽  
D. A. A. Vignali ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Structural Basis ◽  
Cell Responses

scholarly journals Development of a System To Study CD4+-T-Cell Responses to Transgenic Ovalbumin-Expressing Toxoplasma gondii during Toxoplasmosis

2004 ◽  
Vol 72 (12) ◽  
pp. 7240-7246 ◽  
Author(s):  
Marion Pepper ◽  
Florence Dzierszinski ◽  
Amy Crawford ◽  
Christopher A. Hunter ◽  
David Roos
Keyword(s):  
T Cells ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
T Cell Responses ◽  
Cell Receptor ◽  
In Vivo Studies ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT The study of the immune response to Toxoplasma gondii has provided numerous insights into the role of T cells in resistance to intracellular infections. However, the complexity of this eukaryote pathogen has made it difficult to characterize immunodominant epitopes that would allow the identification of T cells with a known specificity for parasite antigens. As a consequence, analysis of T-cell responses to T. gondii has been based on characterization of the percentage of T cells that express an activated phenotype during infection and on the ability of these cells to produce cytokines in response to complex mixtures of parasite antigens. In order to study specific CD4+ T cells responses to T. gondii, recombinant parasites that express a truncated ovalbumin (OVA) protein, in either a cytosolic or a secreted form, were engineered. In vitro and in vivo studies reveal that transgenic parasites expressing secreted OVA are able to stimulate T-cell receptor-transgenic OVA-specific CD4+ T cells to proliferate, express an activated phenotype, and produce gamma interferon (IFN-γ). Furthermore, the adoptive transfer of OVA-specific T cells into IFN-γ−/− mice provided enhanced protection against infection with the OVA-transgenic (but not parental) parasites. Together, these studies establish the utility of this transgenic system to study CD4+-T-cell responses during toxoplasmosis.

Inhibition of human T-cell responses to house dust mite allergens by a T-cell receptor peptide

1994 ◽  
Vol 94 (5) ◽  
pp. 844-852 ◽  
Author(s):  
E JARMAN ◽  
C HAWRYLOWICZ ◽  
E PANAGIOTOPOLOU ◽  
R OHEHIR ◽  
J LAMB
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
House Dust ◽  
House Dust Mite ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Cell Responses ◽  
Human T Cell ◽  
Dust Mite
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