J. Exp. Med., Volume 188, Number 9, November 2, 1998 1669-1678

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

By Andreas Würch, Judit Biro, Alexandre J. Potocnik, Ingrid Falk, Horst Mossmann, and Klaus Eichmann

From the Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany

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 CD48 double negative (DN) thymocytes to the CD4⁺8⁺ 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⁺ 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.

TCR- gene expression;  CD3 complex;  pro-TCR;  thymus;  signaling

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