Ben-Nun A, Liblau R S, Cohen L, Lehmann D, Tournier-Lasserve E, Rosenzweig A, Zhang J W, Raus J C, Bach M A
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2466-70. doi: 10.1073/pnas.88.6.2466.
Recent studies in experimental autoimmune encephalomyelitis as a model for multiple sclerosis (MS) have demonstrated limited heterogeneity in T-cell antigen receptors (TCR) specific for myelin basic protein (MBP). To investigate restricted beta-chain variable-region (V beta) gene usage in humans, we analyzed TCR gene rearrangements in two lines and 34 MBP-specific T-cell clones that were isolated from five MS patients and two healthy subjects. The T cells were characterized for their specificity to MBP epitopes and HLA-restricting molecules. We demonstrate here that MBP-specific T-cell clones from these different MS patients and healthy individuals, in contrast to T cells from rodents, display a more diverse V beta gene usage as evidenced by their TCR V beta gene rearrangements. However, the different MBP-specific T-cell clones isolated from each individual MS patient showed a common V beta gene usage, suggesting individual-specific TCR restriction. Out of 16 MBP-specific clones derived from a single MS patient, 12 clones (75%) utilized the V beta 15 gene for their TCR gene rearrangement. MBP-specific clones isolated from four other MS patients also showed a consistent tendency for a predominant, but different, TCR V beta gene rearrangement. These results suggest a TCR heterogeneity among MBP-specific T-cell clones from different individuals but a limited TCR V beta gene usage among MBP-specific T-cell clones of the same individual. The predominant V beta gene used by the MBP-specific T-cell clones studied here was not found to correlate with the epitope specificity of T cells or with their restricting HLA molecule. These findings may support the possibility of intervention with monoclonal antibodies to specific V beta gene products as an approach to immune therapy of MS but also imply the necessity for an individual-specific immunotherapeutic approach.
近期以实验性自身免疫性脑脊髓炎作为多发性硬化症（MS）模型的研究表明，针对髓鞘碱性蛋白（MBP）的T细胞抗原受体（TCR）存在有限的异质性。为了研究人类中受限的β链可变区（Vβ）基因使用情况，我们分析了从5名MS患者和2名健康受试者中分离出的2个细胞系和34个MBP特异性T细胞克隆中的TCR基因重排。对这些T细胞针对MBP表位和HLA限制性分子的特异性进行了表征。我们在此证明，与啮齿动物的T细胞不同，来自这些不同MS患者和健康个体的MBP特异性T细胞克隆通过其TCR Vβ基因重排显示出更多样化的Vβ基因使用情况。然而，从每位MS患者个体中分离出的不同MBP特异性T细胞克隆显示出共同的Vβ基因使用情况，提示存在个体特异性的TCR限制。在来自一名MS患者的16个MBP特异性克隆中，有12个克隆（75%）在其TCR基因重排中使用Vβ15基因。从其他4名MS患者中分离出的MBP特异性克隆也显示出一种一致的趋势，即存在一种占主导但不同的TCR Vβ基因重排。这些结果表明，来自不同个体的MBP特异性T细胞克隆之间存在TCR异质性，但同一患者的MBP特异性T细胞克隆之间Vβ基因使用情况有限。本文研究的MBP特异性T细胞克隆所使用的占主导的Vβ基因未发现与T细胞的表位特异性或其限制性HLA分子相关。这些发现可能支持使用针对特定Vβ基因产物的单克隆抗体进行干预作为MS免疫治疗方法的可能性，但也意味着需要一种个体特异性的免疫治疗方法。
