Structure and function of the pre-T cell receptor.
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.
von Boehmer
H
H
Institut Necker, INSERM 373, Paris, France.
Fehling
H J
HJ
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation; D002874:Chromosome Mapping; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D017252:CD3 Complex; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha