A permissive geometry model for TCR-CD3 activation

Trends Biochem Sci. 2008 Feb;33(2):51-7. doi: 10.1016/j.tibs.2007.10.008. Epub 2008 Jan 16.


The T cell antigen receptor (TCR-CD3) is the most complex receptor known to date, consisting of eight transmembrane subunits. Its activation by an antigen is the initial step in an immune response. Here, we present the permissive geometry model explaining how antigen binding initiates intracellular signalling cascades. We propose that a dimeric antigen imposes its geometry on two TCR-CD3 receptors by simultaneously binding to both. This causes the TCRalphabeta subunits to rotate with respect to each other leading to displacement of the ectodomains of the associated CD3 dimers. This results in a scissor-like movement of the CD3 dimers that opens the cytoplasmic tails for interaction with signalling proteins, thus initiating signalling cascades.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Lymphocyte Activation*
  • Models, Immunological
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Conformation
  • Receptor-CD3 Complex, Antigen, T-Cell / chemistry
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
  • Signal Transduction / physiology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Multiprotein Complexes
  • Receptor-CD3 Complex, Antigen, T-Cell