The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes.
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.
Mingueneau
Michaël
M
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Case 906, Institut National de la Santé et de la Recherche Médicale U631, and Centre National de la Recherche Scientifique UMR6102, 13288 Marseille Cedex 9, France.
Sansoni
Amandine
A
Grégoire
Claude
C
Roncagalli
Romain
R
Aguado
Enrique
E
Weiss
Arthur
A
Malissen
Marie
M
Malissen
Bernard
B
D000818:Animals; D001482:Base Composition; D017252:CD3 Complex / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011392:Proline; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C485468:Cd3e protein, mouse; D011948:Receptors, Antigen, T-Cell; C095148:Sla protein, mouse; D011392:Proline; D016392:Proto-Oncogene Proteins pp60(c-src)