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Publication : Requirement of CD3 complex-associated signaling functions for expression of rearranged T cell receptor beta VDJ genes in early thymic development.

First Author  Würch A Year  1998
Journal  J Exp Med Volume  188
Issue  9 Pages  1669-78
PubMed ID  9802979 Mgi Jnum  J:112046
Mgi Id  MGI:3655421 Doi  10.1084/jem.188.9.1669
Citation  Wurch A, et al. (1998) Requirement of CD3 complex-associated signaling functions for expression of rearranged T cell receptor beta VDJ genes in early thymic development. J Exp Med 188(9):1669-78
abstractText  During alpha beta thymocyte development, the clonotypic alpha beta-T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR-CD3 complex: the pre-TCR, containing a clonotypic TCR-beta chain and invariant pre-Talpha, is expressed on pre-T cells before rearrangement of the TCR-alpha locus. Moreover, clonotype-independent CD3 complexes (CIC) appear on pro-T cells before VDJ rearrangements of TCR-beta genes. The pre-TCR is known to mediate TCR-beta 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 CD3zeta/eta and/or p56(lck), we observe a pronounced reduction in the proportions of CD25(+) DN thymocytes that express intracellular TCR-beta chains. TCR-beta transcripts are reduced in parallel with TCR-beta polypeptide chains whereas no reduction in TCR-beta locus rearrangements could be detected. Wild-type levels of TCR-beta transcripts and of cells expressing TCR-beta polypeptide chains are induced by treatment with anti-CD3epsilon mAb. The data suggest that the initial expression of rearranged TCR-beta 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.
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