The proline-rich sequence of CD3epsilon as an amplifier of low-avidity TCR signaling

J Immunol. 2008 Jul 1;181(1):243-55. doi: 10.4049/jimmunol.181.1.243.


Engagement of peptide-MHC by the TCR induces a conformational change in CD3epsilon that exposes a proline-rich sequence (PRS) and recruits the cytoskeletal adaptor Nck. This event, which precedes phosphorylation of the CD3epsilon ITAM, has been implicated in synapse formation and T cell function. However, there is compelling evidence that responsiveness to TCR ligation is CD3epsilon PRS independent. In this study, we show that the CD3epsilon PRS is necessary for peptide-MHC-induced phosphorylation of CD3epsilon and for recruitment of protein kinase Ctheta to the immune synapse in differentiated CD8+ T lymphocytes. However, whereas these two events are dispensable for functional T cell responsiveness to high-avidity ligands, they are required for responsiveness to low-avidity ones. Thus, in at least certain T cell clonotypes, the CD3epsilon PRS amplifies weak TCR signals by promoting synapse formation and CD3epsilon phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD3 Complex / chemistry
  • CD3 Complex / genetics
  • CD3 Complex / immunology*
  • CD3 Complex / metabolism*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Gene Amplification / genetics*
  • Histocompatibility Antigens / immunology
  • Immunity, Innate / immunology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptides / pharmacology
  • Phosphorylation
  • Proline / genetics
  • Proline / metabolism
  • Protein Binding
  • Protein Kinase C / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • CD3 Complex
  • Histocompatibility Antigens
  • Peptides
  • Receptors, Antigen, T-Cell
  • Proline
  • Protein Kinase C