Article abstract
Nature Immunology 9, 522 - 532 (2008)
Published online: 13 April 2008 | doi:10.1038/ni.1608
The proline-rich sequence of CD3
controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes
Michaël Mingueneau1, Amandine Sansoni1, Claude Grégoire1, Romain Roncagalli1, Enrique Aguado1,3, Arthur Weiss2, Marie Malissen1 & Bernard Malissen1
Abstract
Antigen recognition by T cell antigen receptors (TCRs) is thought to 'unmask' a proline-rich sequence (PRS) present in the CD3
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 CD3 PRS had no effect on mature T cell responsiveness. In contrast, in preselection CD4+CD8+ thymocytes, the CD3 PRS acted together with the adaptor protein SLAP to promote CD3
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 CD3 PRS enhanced TCR sensitivity to weak ligands. Our results identify previously unknown functions for the evolutionarily conserved CD3 PRS at the CD4+CD8+ developmental stage and suggest a rather limited function in mature T cells.
- 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.
- Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA.
- Present address: Hospital Universitario de Puerto Real, Unidad de Investigación, Carretera Nacional IV Km. 665, Cádiz, Spain.
Correspondence to: Bernard Malissen1 e-mail: bernardm@ciml.univ-mrs.fr
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