Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation

J Immunol. 2004 Mar 15;172(6):3662-9. doi: 10.4049/jimmunol.172.6.3662.


A hallmark of T cell activation is the ligation-induced down-modulation of the TCR:CD3 complex. However, little is known about the molecular events that drive this process. The CD3 zeta-chain has been shown to play a unique role in regulating the assembly, transport, and cell surface expression of the TCR:CD3 complex. In this study we have investigated the relationship between CD3zeta and the TCRalphabetaCD3epsilondeltagamma complex after ligation by MHC:peptide complexes. Our results show that there is a significant increase in free surface CD3zeta, which is not associated with the TCR:CD3 complex, after T cell stimulation. This may reflect dissociation of CD3zeta from the TCRalphabetaCD3epsilondeltagamma complex or transport of intracellular CD3zeta directly to the cell surface. We also show that MHC:peptide ligation also results in exposure of the TCR-associated CD3zeta NH2 terminus, which is ordinarily buried in the complex. These observations appears to be dependent on Src family protein tyrosine kinases, which are known to be critical for efficient T cell activation. These data suggest a mechanism by which ligated TCR may be differentiated from unligated TCR and selectively down-modulated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biotinylation
  • CD3 Complex / metabolism
  • CD3 Complex / physiology
  • Extracellular Space / immunology
  • Extracellular Space / metabolism
  • Humans
  • Hybridomas
  • Ligands
  • Major Histocompatibility Complex / immunology*
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism*
  • Peptide Fragments / physiology
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / physiology
  • Receptor-CD3 Complex, Antigen, T-Cell / antagonists & inhibitors
  • Receptor-CD3 Complex, Antigen, T-Cell / biosynthesis
  • Receptor-CD3 Complex, Antigen, T-Cell / genetics
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • src-Family Kinases / physiology


  • CD3 Complex
  • CD3 antigen, zeta chain
  • Ligands
  • Peptide Fragments
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • src-Family Kinases