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Inefficient V(D)J recombination underlies monogenic T cell receptor β expression.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-08-04 , DOI: 10.1073/pnas.2010077117
Glendon S Wu 1, 2 , Craig H Bassing 2, 3
Affiliation  

The assembly of T cell receptor (TCR) and immunoglobulin (Ig) genes by V(D)J recombination generates the antigen receptor (AgR) diversity that is vital for adaptive immunity. At most AgR loci, V(D)J recombination is regulated so that only one allele assembles a functional gene, ensuring that nearly every T and B cell expresses a single type, or specificity, of AgR. The genomic organizations of some AgR loci permit the assembly and expression of two distinct genes on each allele; however, this is prevented by undetermined mechanisms. We show that the poor qualities of recombination signal sequences (RSSs) flanking Vβ gene segments suppress the assembly and expression of two distinct TCRβ genes from a single allele. Our data demonstrate that an intrinsic genetic mechanism that stochastically limits Vβ recombination efficiency governs monogenic TCRβ expression, thereby restraining the expression of multiple AgRs on αβ T cells.



中文翻译:

低效的V(D)J重组是单基因T细胞受体β表达的基础。

通过V(D)J重组组装T细胞受体(TCR)和免疫球蛋白(Ig)基因可产生对于适应性免疫至关重要的抗原受体(AgR)多样性。在大多数AgR基因座中,V(D)J重组受到调控,因此只有一个等位基因可组装一个功能基因,从而确保几乎每个T细胞和B细胞都表达单一类型或特异性的AgR。一些AgR基因座的基因组组织允许在每个等位基因上组装和表达两个不同的基因。但是,这是由不确定的机制阻止的。我们表明,侧翼Vβ基因片段的重组信号序列(RSSs)的质量较差会抑制单个等位基因的两个不同TCRβ基因的装配和表达。

更新日期:2020-08-05
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