THE CD3-GAMMA-DELTA-EPSILON AND CD3-ZETA ETA MODULES ARE EACH ESSENTIAL FOR ALLELIC EXCLUSION AT THE T-CELL RECEPTOR-BETA LOCUS BUT ARE BOTH DISPENSABLE FOR THE INITIATION OF V TO (D)J RECOMBINATION AT THE T-CELL RECEPTOR-BETA, RECEPTOR-GAMMA, AND RECEPTOR-DELTA LOCI/

The pre-T cell receptor (TCR) associates with CD3-transducing subunits and tri selective expansion and maturation of T cell precursors expre ssing a TCR-beta chain. Recent experiments in pre-T alpha chain-defici ent mice have suggested that the pre-TCR may not be required for signa ling allelic exclusion at the TCR-beta locus. Using CD3-epsilon- and C D3-zeta/eta-deficient mice harboring a productively rearranged TCR-bet a transgene, we showed that the CD3-gamma delta epsilon and CD3-zeta/e ta modules, and by inference the pre-TCR/CD3 complex, are each essenti al for the establishment of allelic exclusion at the endogenous TCR-be ta locus. Furthermore, using mutant mice lacking both the CD3-epsilon and CD3-zeta/eta 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-beta, TCR-gamma, and TCR-delta loci. Thus, the CD3 components are differentially involved in the sequentia l events that make the TCR-beta locus first accessible to, and later i nsulated from, the action of the V(D)J recombinase.