T cell antigen receptor (TCR) must distinguish between abundant irrelevant peptide and antigenic peptide bound to major histocompatibility complex (MHC) molecules. In eLife, Groves and colleagues use live TCR-transgenic T cells on a supported lipid bilayer to image the triggering of individual TCR-peptide-MHC complexes. Triggering is determined by recruitment of the signaling molecule Zap70 to TCRs. Free peptide-MHC moves rapidly and randomly, but after engagement of the TCR, the movement becomes slow and linear, consistent with cytoskeletal involvement. Single TCR-peptide-MHC conjugates are stable, lasting up to tens of seconds, and bind at a stoichiometry of 1:1, yet are still able to recruit Zap70. This suggests that clustering or multimerization of receptors is not a requirement for TCR triggering. The stability of individual conjugates and the 1:1 stoichiometry therefore indicate that signal amplification must take place after TCR triggering.

eLife (3 July 2013) doi:10.7554/eLife.00778