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

Michaël Mingueneau (1) , Amandine Sansoni (1) , Claude Grégoire (1) , Romain Roncagalli (1) , Enrique Aguado (1) , Arthur Weiss (2) , Marie Malissen (1) , Bernard Malissen (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 Department of Medicine, Rosalind Russell Medical Research Center for Arthritis

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.

Domaines: Immunologie

Michaël Mingueneau, Amandine Sansoni, Claude Grégoire, Romain Roncagalli, Enrique Aguado, et al.. The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes.. Nature Immunology, 2008, 9 (5), pp.522-32. ⟨10.1038/ni.1608⟩. ⟨hal-00294188⟩