SELECTION IS NOT REQUIRED TO PRODUCE INVARIANT T-CELL RECEPTOR GAMMA-GENE JUNCTIONAL SEQUENCES
SELECTION IS NOT REQUIRED TO PRODUCE INVARIANT T-CELL RECEPTOR GAMMA-GENE JUNCTIONAL SEQUENCES
复制标题
DOI：
10.1038/362158a0
复制
发表时间：
1993-03-11
期刊：
影响因子：
64.8
通讯作者：
RAULET, DH
中科院分区：
文献类型：
--
作者：
ASARNOW, DM;CADO, D;RAULET, DH
V-、D-和J-基因片段的重组可以产生巨大多样性的T细胞抗原受体（TCR）基因序列1，2。尽管许多γ δ T细胞充分利用了这一多样化过程，但表皮和阴道上皮中的γ δ T细胞并不主要表达恒定的γ δ受体，其中几乎所有生产性重排中的V-（D）-J连接序列都是相同的。认为这些部位的细胞几乎完全使用相同的TCR反映了应激诱导的自体抗原的识别5 -8。为了解释不变连接序列的普遍性，有人提出胸腺选择作用于最初不同的祖细胞群体，导致同质的谱系9，10。或者，不变序列可能是由这些细胞的胎儿胸腺祖细胞中重组机制的偏差引起的8，11，12。我们在这里报告的使用突变的TCR γ基因重排底物已被引入作为转基因的小鼠直接证明，典型的TCR Vgamma 3-Jgamma 1和Vgamma 4-Jgamma 1序列出现在高频率的蛋白质产物的选择的可能性的情况下。
RECOMBINATION of V-, D- and J-gene segments can generate an enormous diversity of T-cell antigen receptor (TCR) gene sequences1,2. Although many gammadelta T cells fully exploit this diversification process, those in the epidermal and vaginal epithelium do not3,4, predominantly expressing invariant gammadelta receptors in which the V-(D)-J junctional sequences in almost all the productive rearrangements are identical. The almost exclusive use of identical TCRs by cells in these sites is thought to reflect recognition of a stress-induced autologous antigen5-8. To explain the prevalence of the invariant junctional sequences, it has been proposed that thymic selection operates on a population of originally diverse progenitor cells, resulting in a homogeneous repertoire9,10. Alternatively the invariant sequences may result from biases in the recombination machinery in the fetal thymic progenitors of these cells8,11,12. We report here the use of mice into which mutated TCR gamma-gene rearrangement substrates have been introduced as transgenes to demonstrate directly that the canonical TCR Vgamma3-Jgamma1 and Vgamma4-Jgamma1 sequences occur at high frequency in the absence of the possibility of selection for the protein products.