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

Nat Immunol. 2008 May;9(5):522-32. doi: 10.1038/ni.1608. Epub 2008 Apr 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Composition
  • CD3 Complex / genetics*
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4 Antigens / analysis
  • CD8 Antigens / analysis
  • Cell Differentiation
  • Gene Deletion
  • Gene Expression Regulation
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proline
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Thymus Gland / immunology


  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Cd3e protein, mouse
  • Receptors, Antigen, T-Cell
  • Sla protein, mouse
  • Proline
  • Proto-Oncogene Proteins pp60(c-src)