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- Title
The proline-rich sequence of CD3ε controls T cell antigen receptor expression on and signaling potency in preselection CD4<sup>+</sup>CD8<sup>+</sup> thymocytes.
- Authors
Mingueneau, Michaël; Sansoni, Amandine; Grégoire, Claude; Roncagalli, Romain; Aguado, Enrique; Weiss, Arthur; Malissen, Marie; Malissen, Bernard
- Abstract
Antigen recognition by T cell antigen receptors (TCRs) is thought to 'unmask' a proline-rich sequence (PRS) present in the CD3ε 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 CD3ε PRS had no effect on mature T cell responsiveness. In contrast, in preselection CD4+CD8+ thymocytes, the CD3ε PRS acted together with the adaptor protein SLAP to promote CD3ζ 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 CD3ε PRS enhanced TCR sensitivity to weak ligands. Our results identify previously unknown functions for the evolutionarily conserved CD3ε PRS at the CD4+CD8+ developmental stage and suggest a rather limited function in mature T cells.
- Publication
Nature Immunology, 2008, Vol 9, Issue 5, p522
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1608