Function of the TCR alpha enhancer in alpha beta and gamma delta T cells
Function of the TCR alpha enhancer in alpha beta and gamma delta T cells
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DOI：
10.1016/s1074-7613(00)80372-6
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发表时间：
1997-10-01
期刊：
影响因子：
32.4
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
Sleckman, BP;Bardon, CG;Alt, FW
我们已经使用基因靶向突变方法来评估T细胞受体α（TCR α）增强子（E α）在TCR α控制中的作用。以及TCR δ基因重排和表达。我们表明，E α功能顺式促进V α到J α重排在整个J α基因座，距离大于70 kb。我们还表明，E α是所需的正常α β T细胞的发展，在这个谱系中，E α是所需的生殖系J α的表达，重排的V α J α基因的正常表达水平，并为不同的V α剧目的表达。在γ δ T细胞中，V δ DJ δ重排不需要E α，但令人惊讶的是，成熟V δ DJ δ转录物的正常表达水平和生殖系J α转录物的表达需要E α。我们的研究结果表明，E α功能不限于TCR α/δ基因座的TCR α组分或α β谱系;相反，E α功能在α β和γ δ谱系T细胞中都很重要。
We have used gene targeted mutational approaches to assess the role of the T cell receptor alpha (TCR alpha) enhancer (E alpha) in the control of TCR alpha. and TCR delta gene rearrangement and expression. We show that E alpha functions in cis to promote V alpha to J alpha rearrangement across the entire J alpha locus, a distance of greater than 70 kb. We also show that E alpha is required for normal alpha beta T cell development; in this lineage, E alpha is required for germline J alpha expression, for normal expression levels of rearranged V alpha J alpha genes, and for expression of a diverse V alpha repertoire. In gamma delta T cells, E alpha is not required for V delta DJ delta rearrangement, but, surprisingly, is required for normal expression levels of mature V delta DJ delta transcripts and for expression of germline J alpha transcripts. Our findings imply that E alpha function is not limited to the TCR alpha components of the TCR alpha/delta locus or to the alpha beta lineage; rather, E alpha function is important in both alpha beta and gamma delta lineage T cells.