期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：7
页码：3882-3887
DOI：10.1073/pnas.96.7.3882
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：During {beta} thymocyte development, clonotype-independent CD3 complexes are expressed at the cell surface before the pre-T cell receptor (TCR). Signaling through clonotype-independent CD3 complexes is required for expression 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 established. We investigated the putative contribution of clonotype-independent CD3 complex signaling to TCR{beta} locus allelic exclusion in mice single-deficient or double-deficient for CD3{zeta}/{eta} and/or p56lck. These mice display defects in the expression of endogenous TCR{beta} genes in immature thymocytes, proportional to the severity of CD3 complex malfunction. Exclusion of endogenous TCR{beta} VDJ (variable, diversity, joining) rearrangements by a functional TCR{beta} transgene was severely compromised in the single-deficient and double-deficient mutant mice. In contrast to wild-type mice, most of the CD25+ double-negative (DN) thymocytes of the mutant mice failed 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 transgene expressed endogenous TCR{beta} polypeptide chains. Many double-positive cells of the mutant mice coexpressed endogenous and transgenic TCR{beta} chains or more than one endogenous TCR{beta} chain. The data suggest that signaling through clonotype-independent CD3 complexes may contribute to allelic exclusion of the TCR{beta} locus by inducing the expression of rearranged TCR{beta} genes in CD25+ DN thymocytes.
关键词：thymus ; T cell development ; CD3ζ ; p56lck ; clonotype-independent CD3 complexes
