T cell receptor γ gene regulatory sequences prevent the function of a novel TCRγ/pTα pre-T cell receptor
T cell receptor γ gene regulatory sequences prevent the function of a novel TCRγ/pTα pre-T cell receptor
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DOI：
10.1016/s1074-7613(00)80576-2
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发表时间：
1998-06-01
期刊：
影响因子：
32.4
通讯作者：
Raulet, DH
中科院分区：
文献类型：
--
作者：
Kang, JS;Fehling, HJ;Raulet, DH
在RAG-1(-/-)小鼠中表达TCRγ基因导致了数量有限的CD4(+)CD8(+)(DP)胸腺细胞的发育。在体内，用抗TCRγ抗体处理后，DP胸腺细胞的数量增加，表明TCR伽马链在细胞表面表达，而不存在增量链、α链或β链。PTα或CD3 epsilon基因突变可阻断转基因诱导的DP细胞发育，提示TCRγ可与PTα和CD3结合形成新的前TCR。在含有额外调控序列的转基因后，TCR-γ在DP细胞中的表达下调，并且DP细胞几乎没有发育。因此，内源性TCRγ/PTα的功能受到通常伴随DP细胞发育的TCRγ基因转录下调的限制。
Expression of a TCR gamma transgene in RAG-1(-/-) mice resulted in the development of a limited number of CD4(+)CD8(+) (DP) thymocytes. In vivo treatments with anti-TCR gamma antibody enhanced the number of DP thymocytes, demonstrating that TCR gamma chains were expressed on the cell surface in the absence of delta, alpha, or beta chains. Mutations in pT alpha or CD3 epsilon genes abolished transgene-induced DP cell development, indicating that TCR gamma can associate with pT alpha and CD3 to form a novel pre-TCR. With a transgene containing additional regulatory sequences, TCR gamma expression was downregulated in DP cells, and little DP cell development occurred. Thus, the function of the endogenous TCR gamma/pT alpha is limited by the transcriptional down-regulation of TCR gamma genes that normally accompanies DP cell development.