Myelin-associated oligodendrocytic basic protein: Identification of an encephalitogenic epitope and association with multiple sclerosis

Myelin-associated oligodendrocytic basic protein (MOBP) is an abundant myelin constituent expressed exclusively by oligodendrocytes, the myelin-forming cells of the CNS,We report that MOBP causes experimental allergic encephalomyelitis and is associated with multiple sclerosis, First, we note that purified recombinant MOBP inoculated into SJL/J mice produces CNS disease, Tests of overlapping peptides spanning the murine MOBP molecule map the encephalitogenic site to-amino acids 37-60, MOBP-induced experimental allergic encephalomyelitis shows a severe clinical course and is characterized by a prominent CD4(+) T lymphocyte infiltration and a lesser presence of CD8(+) T cells and microglia/macrophages around vessels and in the white matter of the CNS, Second, PBL obtained from patients with relapsing/remitting multiple sclerosis mount a proliferative response to human MOBP, especially at amino acids 21-39, This response equals or exceeds the response to myelin basic protein and an influenza virus hemagglutinin peptide, both serving as internal controls. Thus, a novel myelin Ag, MOBP aa 37-60, plays a role in rodent autoimmune CNS disease, and its human MOBP counterpart is associated with the human demyelinating disease multiple sclerosis.