Cooperativity between T cell receptor complexes revealed by conformational mutants of CD3epsilon

Sci Signal. 2009 Aug 11;2(83):ra43. doi: 10.1126/scisignal.2000402.


The CD3epsilon subunit of the T cell receptor (TCR) complex undergoes a conformational change upon ligand binding that is thought to be important for the activation of T cells. To study this process, we built a molecular dynamics model of the transmission of the conformational change within the ectodomains of CD3. The model showed that the CD3 dimers underwent a stiffening effect that was funneled to the base of the CD3epsilon subunit. Mutation of two relevant amino acid residues blocked transmission of the conformational change and the differentiation and activation of T cells. Furthermore, this inhibition occurred even in the presence of excess endogenous CD3epsilon subunits. These results emphasize the importance of the conformational change in CD3epsilon for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes.

MeSH terms

  • Animals
  • CD3 Complex / chemistry
  • CD3 Complex / genetics
  • CD3 Complex / metabolism*
  • Lymphocyte Activation*
  • Mice
  • Models, Molecular
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Protein Conformation
  • Receptors, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell / metabolism


  • CD3 Complex
  • Cd3e protein, mouse
  • Mutant Proteins
  • Receptors, Antigen, T-Cell