Krangel Michael S
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Curr Opin Immunol. 2009 Apr;21(2):133-9. doi: 10.1016/j.coi.2009.03.009. Epub 2009 Apr 9.
The four T cell receptor genes (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs during intrathymic T cell development. These programs depend on genetic factors, including gene segment order and recombination signal sequences. They also depend on epigenetic factors. Regulated changes in chromatin structure, directed by enhancers and promoter, can modify the availability of recombination signal sequences to the RAG recombinase. Regulated changes in locus conformation may control the synapsis of distant recombination signal sequences, and regulated changes in subnuclear positioning may influence locus recombination events by unknown mechanisms. Together these influences may explain the ordered activation and inactivation of T cell receptor locus recombination events and the phenomenon of Tcrb allelic exclusion.
四个T细胞受体基因(Tcra、Tcrb、Tcrg、Tcrd)在胸腺内T细胞发育过程中通过V(D)J重组按照不同程序进行组装。这些程序取决于遗传因素,包括基因片段顺序和重组信号序列。它们还取决于表观遗传因素。由增强子和启动子指导的染色质结构的调控变化,可以改变重组信号序列对RAG重组酶的可用性。基因座构象的调控变化可能控制远距离重组信号序列的联会,而核内亚定位的调控变化可能通过未知机制影响基因座重组事件。这些影响共同作用,可能解释了T细胞受体基因座重组事件的有序激活和失活以及Tcrb等位基因排斥现象。