IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses
書誌事項
- 公開日
- 2020-06-02
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s41467-020-16471-7
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title> <jats:p> 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 <jats:italic>ζ</jats:italic> complex, while maintaining CD3 <jats:italic>ζ</jats:italic> 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 <jats:italic>ζ</jats:italic> complex, yet compromises overall CD3 <jats:italic>ζ</jats:italic> 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. </jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 11 (1), 2779-, 2020-06-02
Springer Science and Business Media LLC