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© Institut Pasteur - Photo by Perrine Bomme, Lise Chauveau & Olivier Schwartz, colorized by Jean-Marc Panaud
Cellule dendritique vue en microscopie électronique à balayage. Les cellules dendritiques sont cellules importantes de l'immunité. Elles sont indispensables à la mise en place de défenses contre les agents infectieux, les tumeurs ou les maladies auto-immunes. Elles interviennent également dans les processus de tolérance de greffes.
Publication : Nature communications

IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 02 Jun 2020

Evnouchidou I, Chappert P, Benadda S, Zucchetti A, Weimershaus M, Bens M, Caillens V, Koumantou D, Lotersztajn S, van Endert P, Davoust J, Guermonprez P, Hivroz C, Gross DA, Saveanu L

Link to Pubmed [PMID] – 32487999

Link to DOI – 10.1038/s41467-020-16471-7

Nat Commun 2020 Jun; 11(1): 2779

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-CD3ζ complex, while maintaining CD3ζ 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-CD3ζ complex, yet compromises overall CD3ζ 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.