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The CD3- and CD3-/ Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor β Locus but Are Both Dispensable for the Initiation of V to (D)J Recombination at the T Cell Receptor–β, –, and – Loci

From the Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale–Centre National de la Recherche Scientifique de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France

The pre–T cell receptor (TCR) associates with CD3-transducing subunits and triggers the selective expansion and maturation of T cell precursors expressing a TCR-β chain. Recent experiments in pre-T chain-deficient mice have suggested that the pre-TCR may not be required for signaling allelic exclusion at the TCR-β locus. Using CD3-– and CD3-/–deficient mice harboring a productively rearranged TCR-β transgene, we showed that the CD3- and CD3-/ modules, and by inference the pre-TCR/CD3 complex, are each essential for the establishment of allelic exclusion at the endogenous TCR-β locus. Furthermore, using mutant mice lacking both the CD3- and CD3-/ genes, we established that the CD3 gene products are dispensable for the onset of V to (D)J recombination (V, variable; D, diversity; J, joining) at the TCR-β, TCR-, and TCR- loci. Thus, the CD3 components are differentially involved in the sequential events that make the TCR-β locus first accessible to, and later insulated from, the action of the V(D)J recombinase.

¹ Abbreviations used in this paper: D, diversity; DN, double negative; DP, double positive; J, joining; PBS/FCS, PBS supplemented with 3% FCS; RAG, recombination activation gene; SP, single positive; V, variable.

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