Requirement of CD3 Complex-associated Signaling Functions for Expression of Rearranged T Cell Receptor   VDJ Genes in Early Thymic Development (original) (raw)

During ␣␤ thymocyte development, the clonotypic ␣␤ -T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR-CD3 complex: the pre-TCR, containing a clonotypic TCR-␤ chain and invariant pre-T ␣ , is expressed on pre-T cells before rearrangement of the TCR-␣ locus. Moreover, clonotype-independent CD3 complexes (CIC) appear on pro-T cells before VDJ rearrangements of TCR-␤ genes. The pre-TCR is known to mediate TCR-␤ selection, the prerequisite for maturation of CD4 Ϫ 8 Ϫ double negative (DN) thymocytes to the CD4 ϩ 8 ϩ double positive stage. A developmental function of CIC has so far not been delineated. In mice single deficient and double deficient for CD3 / and/or p56 lck , we observe a pronounced reduction in the proportions of CD25 ϩ DN thymocytes that express intracellular TCR-␤ chains. TCR-␤ transcripts are reduced in parallel with TCR-␤ polypeptide chains whereas no reduction in TCR-␤ locus rearrangements could be detected. Wild-type levels of TCR-␤ transcripts and of cells expressing TCR-␤ polypeptide chains are induced by treatment with anti-CD3 ⑀ mAb. The data suggest that the initial expression of rearranged TCR-␤ VDJ genes in pro-T cell to pre-T cell progression is dependent on CD3 complex signaling, and thus define a putative developmental function for CIC.