Disruption of extracellular interactions impairs T cell receptor-CD3 complex stability and signaling

Immunity. 2007 Mar;26(3):357-69. doi: 10.1016/j.immuni.2007.01.015.

Abstract

The alphabeta T cell antigen receptor (TCR), in complex with the CD3deltavarepsilon, gammavarepsilon, and zetazeta signaling subunits, is the chief determinant for specific CD4(+) and CD8(+) T cell responses to self and foreign antigens. Although transmembrane domain charge interactions are critical for the assembly of the complex, the location of extracellular contacts between the TCR and CD3 subunits and their contributions to stability and signal transduction have not been defined. Here we used mutagenesis to demonstrate that the CD3deltavarepsilon and CD3gammavarepsilon subunits interact with the TCR via adjacent Calpha DE and Cbeta CC' loops, respectively. The TCR-CD3deltavarepsilon interactions helped stabilize CD3gammavarepsilon within the complex and were important for normal T cell and thymocyte responses to TCR engagement. These data demonstrate that extracellular TCR-CD3 subunit interactions contribute to the structural integrity and function of this multisubunit receptor.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • CD3 Complex / chemistry
  • CD3 Complex / genetics
  • CD3 Complex / immunology*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Protein Structure, Tertiary
  • Protein Subunits
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Signal Transduction
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Tumor Cells, Cultured

Substances

  • CD3 Complex
  • Protein Subunits
  • Receptors, Antigen, T-Cell, alpha-beta