Regulation of T cell receptor (TCR) beta gene expression by CD3 complex signaling in immature thymocytes: Implications for TCR beta allelic exclusion

During alpha beta thymocyte development, clonotype-independent CD3 complexe s are expressed at the cell surface before the pre-T cell receptor (TCR), S ignaling through clonotype-independent CD3 complexes is required for expres sion of rearranged TCR beta genes, On expression of a TCR beta polypeptide chain, the pre-TCR is assembled, and TCR beta locus allelic exclusion is es tablished, We investigated the putative contribution of clonotype-independe nt CD3 complex signaling to TCR beta locus allelic exclusion in mice single -deficient or double-deficient for CD3 zeta/eta and/or p56(lck). These mice display defects in the expression of endogenous TCR beta genes in immature thymocytes, proportional to the severity of CD3 complex malfunction. Exclu sion of endogenous TCR beta VDJ (variable, diversity, joining) rearrangemen ts by a functional TCR beta transgene was severely compromised in the singl e-deficient and double-deficient mutant mice. In contrast to wild-type mice , most of the CD25(+) double-negative (DN) thymocytes of the mutant mice fa iled to express the TCR beta transgene, suggesting defective expression of the TCR beta transgene similar to endogenous TCR beta genes. In the mutant mice, a proportion of CD25+ DN thymocytes that failed to express the transg ene expressed endogenous TCR beta polypeptide chains. Many double-positive cells of the mutant mice coexpressed endogenous and transgenic TCR beta cha ins or more than one endogenous TCR beta chain. The data suggest that signa ling through clonotype-independent CD3 complexes may contribute to allelic exclusion of the TCR beta locus by inducing the expression of rearranged TC R beta genes in CD25(+) DN thymocytes.