| 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: http://dx.doi.org/10.1093/intimm/dxv059 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63137 |
| 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)
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