Ordered and coordinated rearrangement of the TCR α locus:: Role of secondary rearrangement in thymic selection

Ordered and coordinated rearrangement of the TCR α locus:: Role of secondary rearrangement in thymic selection
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DOI:
10.4049/jimmunol.166.4.2597
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发表时间:
2001-02-15
影响因子:
4.4
通讯作者:
Kanagawa, O
Kanagawa, O
中科院分区:
医学2区
文献类型:
--
作者:
Huang, CY;Kanagawa, O

文献摘要

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T淋巴细胞的Ag受体由α β异二聚体组成。α链和β链都是在各自基因座上编码的V(D)J区段的体细胞重排的产物。在T细胞发育期间,P链重排先于iv链重排。等位基因排斥的机制确保了每个T细胞中单个P链的表达,而大量T细胞表达两个功能性Lu链。在这里,我们证明的证据表明,TCR α重排是通过重新安排一个3 ' V α节段和5 ' J α节段在两条染色体上。然后通过使用上游V α和下游J α片段进行重排,直到其被成功的阳性选择终止。这种有序和协调的重排允许单个胸腺细胞顺序表达具有不同特异性的多种TCR,以优化阳性选择的效率。因此,缺乏等位基因排斥和TCR α二级重排在功能性T细胞库的形成中起关键作用。免疫学杂志,2001,166:2597-2601.
The Ag receptor of the T lymphocyte is composed of an alpha beta heterodimer. Both alpha- and beta -chains are products of the somatic rearrangement of V(D)J segments encoded on the respective loci, During T cell development, P-chain rearrangement precedes iv-chain rearrangement. The mechanism of allelic exclusion ensures the expression of a single P-chain in each T cell, whereas a large number of T cells express two functional Lu-chains. Here we demonstrate evidence that TCR a rearrangement is initiated by rearranging a 3 ' V alpha segment and a 5 ' J alpha segment on both chromosomes. Rearrangement then proceeds by using upstream V alpha and downstream J alpha segments until it is terminated by successful positive selection, This ordered and coordinated rearrangement allows a single thymocyte to sequentially express multiple TCRs with different specificities to optimize the efficiency of positive selection. Thus, the lack of allelic exclusion and TCR a secondary rearrangement play a key role in the formation of a functional T cell repertoire. The Journal of Immunology, 2001, 166: 2597-2601.