Measles virus-directed responses of CD4+ T lymphocytes in MS patients and healthy individuals

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.