T-cell receptor peptide-MHC interactions: biological lessons from structural studies

Fifteen years have passed since T-cell receptor (TCR) genes were identified (reviewed in [1]). Unlike the situation for antibodies, no direct structural information on the TCR proteins has been available for most of this time. Recently, however, the crystal structures of isolated alpha and beta chains were determined, shortly followed by the determination of the structure of an alpha beta heterodimer. Subsequently, the structures of two TCR peptide-M HC (pMHC) complexes have been reported. The windfall of this, and other more recent structural information, has elucidated some generalizations for TCR binding and recognition of pMHC. The crystal structures have, however, given us very little insight into the mechanisms of signal transduction by the TCR complex and the subsequent events which lead to activation of a T cell. Ultimately, the crystallographic results will be reconciled with experiments from other disciplines for a complete understanding of the molecular events of T cell activation.