Abstract

The pre-T cell receptor (pre-TCR) that minimally consists of the TCR beta chain and the disulfide-linked pre-T cell receptor alpha (pT alpha) chain in association with signal-transducing CD3 molecules rescues from programmed cell death cells with productive TCR beta rearrangements. The pre-TCR induces expansion and differentiation of these cells such that they become TCR alpha beta bearing CD4+8+ thymocytes, which express only a single TCR beta chain and then either die of neglect or--upon TCR-ligand interaction--undergo either positive or negative selection. The newly discovered pT alpha 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 p56lck. Experiments in pT alpha gene-deficient mice show that the pre-TCR has a crucial role in maturation as well as allelic exclusion of alpha beta T cells but is not required for the development of gamma delta-expressing cells. The function of the pre-TCR cannot be fully assumed by an alpha beta TCR that is expressed abnormally early in T cell development.