The short length of the extracellular domain of zeta is crucial for T cell antigen receptor function

Immunol Lett. 2008 Mar 15;116(2):195-202. doi: 10.1016/j.imlet.2007.11.020. Epub 2007 Dec 26.

Abstract

The T cell antigen receptor (TCR-CD3) consists of the pMHC-binding TCRalphabeta heterodimer and the signalling dimers CD3deltaepsilon, CD3gammaepsilon and zetazeta. The very short length of the extracellular domain (EC) of the zeta chain is preserved through evolution, however a rational explanation for this observation has not been elucidated. Here, we show that TCR-CD3 assembly is clearly defective when the murine zeta EC domain is artificially enlarged. Under these conditions, the TCR-CD3 complex is super-competent in transducing activation signals upon engagement. Furthermore, the TCR-CD3 complexes containing enlarged zeta EC domains underwent ligand-induced conformation changes with higher efficiency than TCR-CD3 complexes with an unmodified zeta EC domain. Together these data suggest that a short zeta EC domain is needed to correctly assemble the TCR-CD3 complex. When this domain is enlarged, the resulting TCR-CD3 complex is distorted leading to a hyperactive phenotype and enhanced T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD3 Complex / chemistry*
  • CD3 Complex / immunology*
  • Cell Line
  • Dimerization
  • Gene Expression
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Receptor-CD3 Complex, Antigen, T-Cell / chemistry*
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology*
  • Recombinant Proteins
  • Sequence Alignment
  • Signal Transduction / immunology

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Recombinant Proteins