Publication: The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes.

Publié dans: Nat Immunol 2008 May; 9(5): 522-32

Auteurs: Mingueneau M, Sansoni A, Grégoire C, Roncagalli R, Aguado E, Weiss A, Malissen M, Malissen B

Résumé

Antigen recognition by T cell antigen receptors (TCRs) is thought to ‘unmask’ a proline-rich sequence (PRS) present in the CD3epsilon cytosolic segment, which allows it to trigger T cell activation. Using ‘knock-in’ mice with deletion of the PRS, we demonstrate here that elimination of the CD3epsilon PRS had no effect on mature T cell responsiveness. In contrast, in preselection CD4+CD8+ thymocytes, the CD3epsilon PRS acted together with the adaptor protein SLAP to promote CD3zeta degradation, thereby contributing to downregulation of TCR expression on the cell surface. In addition, analysis of CD4+CD8+ thymocytes of TCR-transgenic mice showed that the CD3epsilon PRS enhanced TCR sensitivity to weak ligands. Our results identify previously unknown functions for the evolutionarily conserved CD3epsilon PRS at the CD4+CD8+ developmental stage and suggest a rather limited function in mature T cells.

Lien vers Pubmed [PMID] – 18408722

Lien vers HAL – hal-00294188

Lien vers le DOI – 10.1038/ni.1608