Pette M, Liebert U G, Göbel U, Grosse-Wilde H, Hartung H P, Toyka K V
Department of Neurology, University of Würzburg, Germany.
Neurology. 1993 Oct;43(10):2019-25. doi: 10.1212/wnl.43.10.2019.
To analyze the antigen specificities of measles virus (MV)-reactive CD4+ T cells in multiple sclerosis (MS) patients as compared with those of healthy donors, we established 492 MV-reactive short-term T-cell lines (TCL) from blood of 12 MS patients (n = 243 TCL) and 12 healthy subjects (n = 249 TCL). We determined antigen specificities of these TCL by proliferative responses to optimal concentrations of recombinant MV structural proteins (MV-SP) and human myelin basic protein (MBP). In both donor groups, there was a dominant reactivity against the MV fusion protein and the MV nucleocapsid protein. However, there was a substantial heterogeneity of T-cellular polypeptide specificities among MS patients as well as among healthy individuals, which was true even in subjects sharing identical HLA-DR and HLA-DQ haplotypes. By comparing the T-cell antigen specificity patterns obtained in both donor populations, we found decreased percentages of TCL reactive with the MV fusion protein, the hemagglutinin, and the phosphoprotein in MS patients, but these differences failed to reach statistical significance. None of the 492 MV-specific TCL, nor an additional 276 TCL, showed any reactivity to MBP. Therefore, we did not detect any MS-specific pattern of T-cell responses to MV-SP. Furthermore, our study suggests that mechanisms other than molecular mimicry between MV-SP and MBP may cause myelin-directed autoimmunity.
为了分析与健康供体相比,多发性硬化症(MS)患者中麻疹病毒(MV)反应性CD4+ T细胞的抗原特异性,我们从12例MS患者的血液(n = 243个TCL)和12名健康受试者的血液(n = 249个TCL)中建立了492个MV反应性短期T细胞系(TCL)。我们通过对重组MV结构蛋白(MV-SP)和人髓鞘碱性蛋白(MBP)的最佳浓度的增殖反应来确定这些TCL的抗原特异性。在两个供体组中,对MV融合蛋白和MV核衣壳蛋白都有主要反应性。然而,MS患者之间以及健康个体之间T细胞多肽特异性存在很大异质性,即使在共享相同HLA-DR和HLA-DQ单倍型的受试者中也是如此。通过比较两个供体群体中获得的T细胞抗原特异性模式,我们发现MS患者中与MV融合蛋白、血凝素和磷蛋白反应的TCL百分比降低,但这些差异未达到统计学意义。492个MV特异性TCL以及另外276个TCL均未显示出对MBP的任何反应性。因此,我们未检测到任何针对MV-SP的MS特异性T细胞反应模式。此外,我们的研究表明,MV-SP和MBP之间分子模拟以外的机制可能导致针对髓鞘的自身免疫。