Regulation of T cell receptor β allelic exclusion at a level beyond accessibility
Regulation of T cell receptor β allelic exclusion at a level beyond accessibility
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DOI：
10.1038/ni1157
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发表时间：
2005-02-01
影响因子：
30.5
通讯作者：
Krangel, MS
中科院分区：
文献类型：
--
作者：
Jackson, A;Kondilis, HD;Krangel, MS
V-β-to-DJ(β)重组的等位基因排斥依赖于双阴性胸腺细胞中编码T细胞受体β基因的等位基因的异步化重排以及在双阳性胸腺细胞中维持的反馈抑制。反馈被认为是通过下调V-beta可及性来实施的。为了推翻这一负面调控，我们将编码T细胞受体α的基因的增强子引入到Vbeta(12)下游的V-beta基因簇中。在双阴性胸腺细胞中，引入的增强子对可及性没有明显影响，但V(Beta)12重排被刺激，V(Beta)12等位基因排斥被部分颠覆。相比之下，双阳性胸腺细胞表现出V-β转录和可及性增加，但V-β-到DJ(β)重组的反馈抑制保持不变。我们的结果表明，对V-beta-to-DJ(Beta)重组的额外监管限制超出了可及性障碍。
Allelic exclusion of V-beta-to- DJ(beta) recombination depends on asynchronous rearrangement of alleles of the gene encoding T cell receptor beta in double-negative thymocytes and feedback inhibition that is maintained in double-positive thymocytes. Feedback is thought to be enforced through downregulation of V-beta accessibility. In an attempt to override this negative regulation, we introduced the enhancer of the gene encoding T cell receptor alpha into the V-beta gene cluster downstream of Vbeta(12). In double-negative thymocytes, the introduced enhancer had no measurable effect on accessibility, but V(beta)12 rearrangement was stimulated and V(beta)12 allelic exclusion was partially subverted. In contrast, double-positive thymocytes showed increased V-beta transcription and accessibility, but feedback inhibition of V-beta-to- DJ(beta) recombination remained intact. Our results indicate additional regulatory constraints on V-beta-to-DJ(beta) recombination that operate beyond the accessibility barrier.