Autor: |
Kamimura, Daisuke, Arima, Yasunobu, Tsuruoka, Mineko, Jiang, Jing-jing, Bando, Hidenori, Meng, Jie, Sabharwal, Lavannya, Stofkova, Andrea, Nishikawa, Naoki, Higuchi, Kotaro, Ogura, Hideki, Atsumi, Toru, Murakami, Masaaki |
Jazyk: |
angličtina |
Rok vydání: |
2016 |
Předmět: |
|
Zdroj: |
International immunology. 28(3):117-126 |
ISSN: |
0953-8178 |
Popis: |
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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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