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- W3030654879 abstract "Abstract 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." @default.
- W3030654879 created "2020-06-05" @default.
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- W3030654879 date "2020-06-02" @default.
- W3030654879 modified "2023-10-17" @default.
- W3030654879 title "IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses" @default.
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- W3030654879 doi "https://doi.org/10.1038/s41467-020-16471-7" @default.
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