Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F16%3A43913128" target="_blank" >RIV/00216208:11120/16:43913128 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1093/intimm/dxv059" target="_blank" >http://dx.doi.org/10.1093/intimm/dxv059</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/intimm/dxv059" target="_blank" >10.1093/intimm/dxv059</a>

Result language

angličtina

Original language name

Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells

Original language description

KDEL receptor 1 (KDELR1) regulates integrated stress responses (ISR) to promote naive T-cell survival in vivo. In a mouse line having nonfunctional KDELR1, T-Red (naive T-cell reduced) mice, polyclonal naive T cells show excessive ISR and eventually undergo apoptosis. However, breeding T-Red mice with TCR-transgenic mice bearing relatively high TCR affinity rescued the T-Red phenotype, implying a link between ISR-induced apoptosis and TCR-mediated signaling. Here, we showed that strong TCR stimulation reduces ISR in naive T cells. In mice lacking functional KDELR1, surviving naive T cells expressed significantly higher levels of CD5, a surrogate marker of TCR self-reactivity. In addition, higher TCR affinity/avidity was confirmed using a tetramer dissociation assay on the surviving naive T cells, suggesting that among the naive T-cell repertoire, those that receive relatively stronger TCR-mediated signals via self-antigens survive enhanced ISR. Consistent with this observation, weak TCR stimulation with altered peptide ligands decreased the survival and proliferation of naive T cells, whereas stimulation with ligands having higher affinity had no such effect. These results suggest a novel role of TCR-mediated signals in the attenuation of ISR in vivo.

Czech name

—

Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EC - Immunology

OECD FORD branch

—

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Immunology

ISSN

0953-8178

e-ISSN

—

Volume of the periodical

28

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

117-126

UT code for WoS article

000372424000002

EID of the result in the Scopus database

2-s2.0-84959916439