Zang Ying C Q, Li Sufang, Rivera Victor M, Hong Jian, Robinson Rachel R, Breitbach Wini T, Killian James, Zhang Jingwu Z
Multiple Sclerosis Research Unit, Department of Neurology and Baylor Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
J Immunol. 2004 Apr 15;172(8):5120-7. doi: 10.4049/jimmunol.172.8.5120.
Autoreactive T cells of CD4 and CD8 subsets recognizing myelin basic protein (MBP), a candidate myelin autoantigen, are thought to contribute to and play distinct roles in the pathogenesis of multiple sclerosis (MS). In this study we identified four MBP-derived peptides that had high binding affinity to HLA-A2 and HLA-A24 and characterized the CD8(+) T cell responses and their functional properties in patients with MS. There were significantly increased CD8(+) T cell responses to 9-mer MBP peptides, in particular MBP(111-119) and MBP(87-95) peptides that had high binding affinity to HLA-A2, in patients with MS compared with healthy individuals. The resulting CD8(+) T cell lines were of the Th1 phenotype, producing TNF-alpha and IFN-gamma and belonged to a CD45RA(-)/CD45RO(+) memory T cell subset. Further characterization indicated that the CD8(+) T cell lines obtained were stained with MHC class I tetramer (HLA-A2/MBP(111-119)) and exhibited specific cytotoxicity toward autologous target cells pulsed with MBP-derived peptides in the context of MHC class I molecules. These cytotoxic CD8(+) T cell lines derived from MS patients recognized endogenously processed MBP and lysed COS cells transfected with genes encoding MBP and HLA-A2. These findings support the potential role of CD8(+) CTLs recognizing MBP in the injury of oligodendrocytes expressing both MHC class I molecules and MBP.
识别髓鞘碱性蛋白（MBP，一种候选髓鞘自身抗原）的CD4和CD8亚群自身反应性T细胞被认为在多发性硬化症（MS）的发病机制中发挥作用并具有不同的功能。在本研究中，我们鉴定出四种与HLA - A2和HLA - A24具有高结合亲和力的MBP衍生肽，并对MS患者的CD8(+) T细胞反应及其功能特性进行了表征。与健康个体相比，MS患者对9聚体MBP肽，特别是与HLA - A2具有高结合亲和力的MBP(111 - 119)和MBP(87 - 95)肽的CD8(+) T细胞反应显著增加。产生的CD8(+) T细胞系具有Th1表型，产生肿瘤坏死因子-α和干扰素-γ，属于CD45RA(-)/CD45RO(+)记忆T细胞亚群。进一步的表征表明，获得的CD8(+) T细胞系用MHC I类四聚体（HLA - A2/MBP(111 - 119)）染色，并在MHC I类分子的背景下对用MBP衍生肽脉冲处理的自体靶细胞表现出特异性细胞毒性。这些源自MS患者的细胞毒性CD8(+) T细胞系识别内源性加工的MBP，并裂解用编码MBP和HLA - A2的基因转染的COS细胞。这些发现支持了识别MBP的CD8(+) CTL在损伤同时表达MHC I类分子和MBP的少突胶质细胞中的潜在作用。
