Developmentally programmed rearrangement of T cell receptor Vγ genes is controlled by sequences immediately upstream of the Vγ genes

Developmentally programmed rearrangement of T cell receptor Vγ genes is controlled by sequences immediately upstream of the Vγ genes
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DOI:
10.1016/s1074-7613(00)80598-1
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发表时间:
1998-08-01
期刊:
影响因子:
32.4
通讯作者:
Raulet, DH
Raulet, DH
中科院分区:
医学1区
文献类型:
--
作者:
Baker, JE;Cado, D;Raulet, DH

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在胸腺发育过程中,表达不同V、γ和V三角链的不同的伽马三角洲T细胞亚群以有序波的形式出现。在小鼠J-Gamma 1-C-Gamma 1基因簇中,V-Gamma 3基因片段最早用于胎儿胸腺发育,是树突状表皮T细胞(DECs)的祖细胞。在胎儿晚期及以后,V-GMA2基因片段主要存在于次级淋巴器官的细胞中。使用转基因TCR伽马重组底物,我们证明了这种限制性的V伽马基因的使用是由发育靶向的基因重排决定的。我们发现,V-Gamma 2和V-Gamma 3基因上游的序列直接指导成人胸腺细胞的重排模式。因此,用于重组的V-伽马基因的选择与伽马三角洲亚群中不同的分化程序相协调。
Distinct subsets of gamma delta T cells expressing different V gamma and V delta chains arise in ordered waves during thymic development. In the murine J gamma 1-C gamma 1 cluster, the V gamma 3 gene segment is utilized earliest in fetal thymic development, in progenitors of dendritic epidermal T cells (DECs). The V gamma 2 gene segment predominates in the late fetal stages and beyond, in cells destined for the secondary lymphoid organs. Using transgenic TCR gamma recombination substrates, we demonstrate that this restricted V gamma gene usage is determined by developmentally targeted gene rearrangement. We show that sequences immediately upstream of the V gamma 2 and V gamma 3 genes direct the rearrangement pattern in adult thymocytes. Thus, the choice of V gamma gene for recombination is coordinated with distinct differentiation programs in gamma delta subsets.