STRUCTURE AND FUNCTION OF THE PRE-T CELL RECEPTOR

▪ Abstract The pre-T cell receptor (pre-TCR) that minimally consists of the TCRβ chain and the disulfide-linked pre-T cell receptor alpha (pTα) chain in association with signal-transducing CD3 molecules rescues from programmed cell death cells with productive TCRβ rearrangements. The pre-TCR induces expansion and differentiation of these cells such that they become TCRαβ bearing CD4 + 8 + thymocytes, which express only a single TCRβ chain and then either die of neglect or—upon TCR-ligand interaction—undergo either positive or negative selection. The newly discovered pTα gene encodes a transmembrane protein that belongs to the Ig superfamily and contains a cytoplasmic tail that, however, has no essential function in signal transduction, which is mediated by CD3 molecules and most likely p56 lck . Experiments in pTα gene–deficient mice show that the pre-TCR has a crucial role in maturation as well as allelic exclusion of αβ T cells but is not required for the development of γδ-expressing cells. The function of the pre-TCR cannot be fully assumed by an αβ TCR that is expressed abnormally early in T cell development.