Dynamics of the reactivity to MBP in multiple sclerosis

Though many lines of evidence support the importance of myelin basic protei n (MBP) in the pathogenesis of experimental autoimmune encephalomyelitis (E AE), its role in multiple sclerosis (MS) is still debated as well as the si gnificance of epitope spreading in disease progression. We characterised th e response to MBP in eight MS subjects and three of these were followed ove r time. In one case, the follow up lasted over a 6-year period. Clonal expa nsion, clonal persistence and epitope spreading against other MBP determina nts was detected irrespective of disease course. In one patient we identifi ed a novel T-cell receptor variable gene (BV28S2) which may be involved in the selection of MBP determinants, as suggested by experiments performed in the presence of mismatched antigen presenting cells (APG) between two subj ects compatible for HLA-DR2 subtype but differing for the epitope recognise d. Our findings do not sustain a role for the response to MBP effecting on clinical course and suggest that a novel TCR gene may be involved in the re cognition of unusual self antigens.