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

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Title: Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells
Other Titles: Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naïve T cells
A link between TCR-mediated signals and stress responses
Authors: Kamimura, Daisuke Browse this author →KAKEN DB
Arima, Yasunobu Browse this author
Tsuruoka, Mineko Browse this author
Jiang, Jing-jing Browse this author
Bando, Hidenori Browse this author
Meng, Jie Browse this author
Sabharwal, Lavannya Browse this author
Stofkova, Andrea Browse this author
Nishikawa, Naoki Browse this author
Higuchi, Kotaro Browse this author
Ogura, Hideki Browse this author →KAKEN DB
Atsumi, Toru Browse this author
Murakami, Masaaki Browse this author →KAKEN DB
Keywords: KDEL receptors
stress responses
T-cell homeostasis
TCR signal
Issue Date: Mar-2016
Publisher: Oxford University Press
Journal Title: International immunology
Volume: 28
Issue: 3
Start Page: 117
End Page: 126
Publisher DOI: 10.1093/intimm/dxv059
PMID: 26489882
Abstract: 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.
Rights: This is a pre-copyedited, author-produced PDF of an article accepted for publication in International Immunology following peer review. The version of record, Int. Immunol. (2016) 28 (3): 117-126, is available online at:
Type: article (author version)
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 上村 大輔

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