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

During β thymocyte development, the clonotypic β–T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR–CD3 complex: the pre-TCR, containing a clonotypic TCR-β 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-β genes. The pre-TCR is known to mediate TCR-β selection, the prerequisite for maturation of CD4^–8^– 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-β chains. TCR-β transcripts are reduced in parallel with TCR-β polypeptide chains whereas no reduction in TCR-β locus rearrangements could be detected. Wild-type levels of TCR-β transcripts and of cells expressing TCR-β polypeptide chains are induced by treatment with anti-CD3 mAb. The data suggest that the initial expression of rearranged TCR-β 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.

Key Words: TCR-β gene expression • CD3 complex • pro-TCR • thymus • signaling

This paper was written while K. Eichmann was a Scholar-in-Residence at the Fogarty International Center for Advanced Study in the Health Sciences, National Institutes of Health, Bethesda, Maryland.

A. Würch and J. Biro contributed equally to this work.

Abbreviations used: BrdU, 5-bromodeoxyuridine; CIC, clonotype-independent CD3 complex; dd, double deficient; DN, double negative; DP, double positive; HPRT, hypoxanthine phosphoribosyltransferase; Lck, p56^lck; RT, reverse transcription; RTOC, reaggregate thymic organ culture; sd, single deficient; wt, wild-type.

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