Antigen ligation triggers a conformational change within the constant domain of the alphabeta T cell receptor

Immunity. 2009 Jun 19;30(6):777-88. doi: 10.1016/j.immuni.2009.03.018. Epub 2009 May 21.


Ligation of the alphabeta T cell receptor (TCR) by a specific peptide-loaded major histocompatibility complex (pMHC) molecule initiates T cell signaling via the CD3 complex. However, the initial events that link antigen recognition to T cell signal transduction remain unclear. Here we show, via fluorescence-based experiments and structural analyses, that MHC-restricted antigen recognition by the alphabeta TCR results in a specific conformational change confined to the A-B loop within the alpha chain of the constant domain (Calpha). The apparent affinity constant of this A-B loop movement mirrored that of alphabeta TCR-pMHC ligation and was observed in two alphabeta TCRs with distinct pMHC specificities. The Ag-induced A-B loop conformational change could be inhibited by fixing the juxtapositioning of the constant domains and was shown to be reversible upon pMHC disassociation. Notably, the loop movement within the Calpha domain, although specific for an agonist pMHC ligand, was not observed with a pMHC antagonist. Moreover, mutagenesis of residues within the A-B loop impaired T cell signaling in an in vitro system of antigen-specific TCR stimulation. Collectively, our findings provide a basis for the earliest molecular events that underlie Ag-induced T cell triggering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / chemistry*
  • Antigens / immunology
  • Humans
  • Major Histocompatibility Complex / immunology
  • Mutation / genetics
  • Peptides / chemistry
  • Peptides / immunology
  • Protein Binding / immunology
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes / immunology*


  • Antigens
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta