Wucherpfennig K W, Ota K, Endo N, Seidman J G, Rosenzweig A, Weiner H L, Hafler D A
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Science. 1990 May 25;248(4958):1016-9. doi: 10.1126/science.1693015.
Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.
多发性硬化症(MS)可能是一种由针对髓鞘蛋白的T细胞介导的自身免疫性疾病。研究表明,在MS患者体内被激活的髓鞘碱性蛋白(MBP)反应性T细胞,这表明MBP可能是MS中的一种靶抗原。在来自MS患者和健康受试者的83个T细胞系中检测了T细胞受体(TCR)β链的可变(V)区,这些T细胞系与人类MBP的免疫显性区(第84至102位氨基酸)或MBP的第二个免疫显性区(143至168位氨基酸)发生反应。在不同个体中,Vβ17以及程度较轻的Vβ12在识别MBP(84 - 102)时经常被使用。相比之下,在与MBP(143 - 168)反应的细胞系中,Vβ17非常少见。这些数据表明,在识别人类自身抗原MBP的免疫显性区时,存在共享的TCR Vβ基因使用情况。这种TCR结构可作为MS特异性免疫治疗的靶点。