STRUCTURE AND FUNCTION OF THE PRE-T CELL RECEPTOR

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  • Harald von Boehmer
    Institut Necker, INSERM 373, 156 rue de Vaugirard, Paris Cedex 15, F-75730 France
  • Hans Jörg Fehling
    Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland

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<jats:p>▪ 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<jats:sup>+</jats:sup>8<jats:sup>+</jats:sup>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<jats:sup>lck</jats:sup>. 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.</jats:p>

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