GENES ENCODING LIGANDS FOR DELETION OF V-BETA-11 T-CELLS COSEGREGATE WITH MAMMARY-TUMOR VIRUS GENOMES
GENES ENCODING LIGANDS FOR DELETION OF V-BETA-11 T-CELLS COSEGREGATE WITH MAMMARY-TUMOR VIRUS GENOMES
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DOI：
10.1038/349531a0
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发表时间：
1991-02-07
期刊：
影响因子：
64.8
通讯作者：
TOMONARI, K
中科院分区：
文献类型：
--
作者：
DYSON, PJ;KNIGHT, AM;TOMONARI, K
胸腺中的T细胞受体(TCR)谱系是在编码TCRα链和β链的基因重排后在胸腺中选择的。选择是基于新出现的T细胞对与主要组织相容性复合体分子相关的自身配体的识别：一些组合导致正选择，另一些组合导致负选择。负选择或克隆性删除是消除自身反应性T细胞的重要机制。一组与克隆缺失有关的自体配体被确定，因为它们像外源超抗原2一样，几乎被所有表达特定TCRV-β基因的T细胞识别。V-beta-17a T细胞被组织特异性配体3，4删除；V-beta-6、V-beta-7、V-beta-8.1和V-beta-9 T细胞被微小淋巴细胞刺激(MLS)决定簇MLS-1a删除(参考文献5-8)；V-beta-3T细胞被MLS-2a和MLS-3a删除(参考文献9，10)；V-beta-11 T细胞由独立分离基因编码的配体删除；利用重组近交系小鼠和经典回交的染色体定位表明，DBA/2小鼠的MLS-1a编码在1号染色体上，V-β-5 T细胞缺失的两个配基基因之一定位在12号染色体上(参考文献12)。12)，V-β-11缺失的配基基因与6号染色体上的CD8基因连锁(参考文献11)。在这里，我们提出了来自三组回交小鼠的证据，证明了6、12和14号染色体上的V-β-11缺失配体基因与内源性小鼠乳腺肿瘤病毒整合蛋白(MTV)基因组之间的一致性。我们的结果表明，V-β-11缺失配体是MTV基因组的产物。
THE T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains 1. Selection is based on the recognition by newly emergent T cells of self-ligands associated with molecules of the major histocompatibility complex: some combinations result in positive selection, others in negative selection. Negative selection, or clonal deletion, is an important mechanism for eliminating autoreactive T cells. A group of self-ligands involved in clonal deletion was identified because they, like exogenous superantigens 2, were recognized by almost all T cells expressing particular TCR V-beta genes. V-beta-17a T cells are deleted by a tissue-specific ligand 3,4; V-beta-6, V-beta-7, V-beta-8.1 and V-beta-9 T cells are deleted by the minor lymphocyte-stimulating (Mls) determinant Mls-1a (refs 5-8); V-beta-3 T cells by Mls-2a and Mls-3a (refs 9,10); V-beta-11 T cells 11 by ligands encoded by independently segregating genes; and V-beta-5 T cells by ligands encoded by two genes 12. Chromosomes mapping using recombinant inbred strains of mice and classic backcrosses show that Mls-1a in DBA/2 mice is encoded on chromosome 1, that one of the two ligand genes for deletion of V-beta-5 T cells maps to chromosome 12 (ref. 12) and that a ligand gene for V-beta-11 deletion is linked to the CD8 locus on chromosome 6 (ref. 11). Here we present evidence from three sets of backcross mice for concordance between V-beta-11 deletion ligand genes on chromosomes 6, 12 and 14 and endogenous mouse mammary tumour virus integrant (Mtv) genomes. Our results indicate that the V-beta-11 deletion ligands are products of Mtv genomes.