Turner S J, Cose S C, Carbone F R
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
J Immunol. 1996 Dec 1;157(11):4979-85.
There is considerable variation in the TCR repertoire diversity selected by different peptide Ags. Certain responses show limited V region bias with minimal restrictions in the remainder of the sequence while others can be dominated by a single TCR clonotype repeatedly isolated from different individuals. CTL specific for a Kb-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 beta-chain subset with extensive conservation located at the V-D junction. However, unlike some biased responses, no single beta-chain V-D-J combination appears to dominate these CTL. Different animals respond with a large array of unique or "private" beta-chain sequences with little J region preference. Here we examine the contribution of the TCR alpha-chain to the gB-specific CTL diversity. The TCR alpha-chains from different TCRBV10-positive gB-specific CTL clones were found to exhibit extensive sequence variation. However, when T cells were forced to use a single alpha-chain in TCR alpha-chain transgenic mice, gB-specific CTL showed limited variation in their beta-chain selection. These T cells retained the TCRBV10 bias but were now dominated by a single beta-chain sequence that could be repeatedly isolated from different transgenic animals. This "public" TCR consisted of the transgenic alpha-chain and a common TCRBV10D2J2S6 beta-chain. These results suggest that preferential use of one TCR subunit can restrict the level of diversity in the other chain due to interchain interactions involving J-derived sequences.
不同肽抗原所选择的TCR库多样性存在相当大的差异。某些反应显示出有限的V区偏向性，序列其余部分的限制最小，而其他反应可能由从不同个体反复分离出的单一TCR克隆型主导。针对单纯疱疹病毒糖蛋白B（gB）的Kb限制性决定簇的CTL优先表达占主导地位的TCRBV10β链亚群，其在V-D连接处具有广泛的保守性。然而，与一些有偏向性的反应不同，似乎没有单一的β链V-D-J组合能主导这些CTL。不同动物以大量独特或“私有”的β链序列做出反应，对J区的偏好很小。在这里，我们研究了TCRα链对gB特异性CTL多样性的贡献。发现来自不同TCRBV10阳性gB特异性CTL克隆的TCRα链表现出广泛的序列变异。然而，当在TCRα链转基因小鼠中迫使T细胞使用单一α链时，gB特异性CTL在其β链选择上显示出有限的变异。这些T细胞保留了TCRBV10偏向性，但现在由一个单一的β链序列主导，该序列可以从不同的转基因动物中反复分离出来。这种“公共”TCR由转基因α链和常见的TCRBV10D2J2S6β链组成。这些结果表明，由于涉及J衍生序列的链间相互作用，优先使用一个TCR亚基会限制另一条链的多样性水平。
