Molecular mechanisms involved in T cell receptor triggering

Despite intensive investigation we still do not understand how the T cell antigen receptor (TCR) tranduces signals across the plasma membrane, a process referred to as TCR triggering. Three basic mechanisms have been proposed, involving aggregation, conformational change, or segregation of the TCR upon binding pMHC ligand. Given the low density of pMHC ligand it remains doubtful that TCR aggregation initiates triggering, although it is likely to enhance subsequent signalling. Structural studies to date have not provided definitive evidence for or against a conformational change mechanism, but they have ruled out certain types of conformational change. Size-induced segregation of the bound TCR from inhibitory membrane tyrosine phosphatases seems to be required, but is probably not the only mechanism. Current evidence suggests that TCR triggering is initiated by a combination of segregation and conformational change, with subsequent aggregation contributing to amplification of the signal.