Dyson P J, Knight A M, Fairchild S, Simpson E, Tomonari K
Clinical Research Centre, Harrow, Middlesex, UK.
Nature. 1991 Feb 7;349(6309):531-2. doi: 10.1038/349531a0.
The T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains. 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, 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; 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; V beta 3 T cells by Mls-2a and Mls-3a; V beta 11 T cells by ligands encoded by independently segregating genes; and V beta 5 T cells by ligands encoded by two genes. Chromosome 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 and that a ligand gene for V beta 11 deletion is linked to the CD8 locus on chromosome 6. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
T细胞受体(TCR)库在编码TCRα和β链的基因重排后于胸腺中被选择。选择基于新出现的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:一些组合导致阳性选择,另一些则导致阴性选择。阴性选择,即克隆清除,是消除自身反应性T细胞的重要机制。一组参与克隆清除的自身配体被确定,因为它们与外源性超抗原一样,几乎被所有表达特定TCR Vβ基因的T细胞识别。Vβ17a T细胞被一种组织特异性配体清除;Vβ6、Vβ7、Vβ8.1和Vβ9 T细胞被次要淋巴细胞刺激(Mls)决定簇Mls-1a清除;Vβ3 T细胞被Mls-2a和Mls-3a清除;Vβ11 T细胞被独立分离基因编码的配体清除;Vβ5 T细胞被两个基因编码的配体清除。使用小鼠重组近交系和经典回交进行的染色体定位表明,DBA/2小鼠中的Mls-1a在1号染色体上编码,用于清除Vβ5 T细胞的两个配体基因之一定位于12号染色体,而用于Vβ11清除的配体基因与6号染色体上的CD8基因座相连。在此,我们提供了来自三组回交小鼠的证据,证明6号、12号和14号染色体上的Vβ11清除配体基因与内源性小鼠乳腺肿瘤病毒整合体(Mtv)基因组之间存在一致性。(摘要截断于250字)