IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses
In: Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723, 2020
Online
academicJournal
Zugriff:
T cell receptor (TCR) activation is modulated by mechanisms such as TCR endocytosis, which is thought to terminate TCR signalling. Here we show that, upon internalization, TCR continues to signal from a set of specialized endosomes that are crucial for T cell functions. Mechanistically, TCR ligation leads to clathrin-mediated internalization of the TCR-CD3 ζ complex, while maintaining CD3 ζ signalling, in endosomal vesicles that contain the insulin responsive aminopeptidase (IRAP) and the SNARE protein Syntaxin 6. Destabilization of this compartment through IRAP deletion enhances plasma membrane expression of the TCR-CD3 ζ complex, yet compromises overall CD3 ζ signalling; moreover, the integrity of this compartment is also crucial for T cell activation and survival after suboptimal TCR activation, as mice engineered with a T cell-specific deletion of IRAP fail to develop efficient polyclonal anti-tumour responses. Our results thus reveal a previously unappreciated function of IRAP-dependent endosomal TCR signalling in T cell activation.
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IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses
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Autor/in / Beteiligte Person: | Evnouchidou, Irini ; Chappert, Pascal ; Benadda, Samira ; Zucchetti, Andres ; Weimershaus, Mirjana ; Bens, Marcelle ; Caillens, Vivien ; Koumantou, Despoina ; Lotersztajn, Sophie ; van Endert, Peter ; Davoust, Jean ; Guermonprez, Pierre ; Hivroz, Claire ; Gross, David A. ; Saveanu, Loredana ; Fondation pour la Recherche Médicale ; Agence Nationale de la Recherche |
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Zeitschrift: | Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723, 2020 |
Veröffentlichung: | Springer Science and Business Media LLC, 2020 |
Medientyp: | academicJournal |
DOI: | 10.1038/s41467-020-16471-7 |
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