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Byline: C. C. A. Bernard (1), T. G. Johns (1), A. Slavin (1), M. Ichikawa (1), C. Ewing (1), J. Liu (1), J. Bettadapura (1) Keywords: Key wordsaMyelin oligodendrocyte glycoprotein; Multiple sclerosis; Experimental autoimmune encephalomyelitis; Demyelination; Autoantigen Abstract: aMyelin oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin superfamily expressed exclusively in central nervous system (CNS) myelin. While the function of MOG is unknown, a number of studies have shown that immune responses to MOG contribute to the autoimmune-mediated demyelination seen in animals immunized with whole CNS tissue. This paper summarizes our recent studies, which unequivocally demonstrate that MOG by itself is able to generate both an encephalitogenic T cell response and an autoantibody response in Lewis rats and in several strains of mice. In Lewis rats the injection of both native MOG and MO[G.sub.35--55 ]peptide produces a paralytic relapsing-remitting neurological disease with extensive plaque-like demyelination. The antibody response to MO[G.sub.35--55 ]was highly restricted, as no reactivity to either other MOG peptides or myelin proteins could be detected. Fine epitope mapping showed that antibody from serum and cerebrospinal fluid of injected rats reacted strongly to MOG.sub.37--46, which is contiguous to the dominant T cell epitope contained within MOG.sub.44--55. NOD/Lt and C57BL/6 mice were also susceptible to severe neurological disease following injection with recombinant MOG or MO[G.sub.35--55 ]peptide, indicating that this specific CNS autoantigen, or some of its determinants, can induce a pathogenic response across animal species. Severe paralysis and extensive demyelination were seen in both strains, but NOD/Lt mice experienced a chronic relapsing disease whereas C57BL/6 mice had a chronic non-remitting disease. Moreover, transfer of MO[G.sub.35--55 ]T cells into naive NOD/Lt mice also produced severe neurological impairment as well as histological lesions. These results emphasize that a synergism between a T cell-response and anti-MOG antibodies may be important for the development of severe demyelinating disease. This, together with our demonstration that there is a predominant T cell response to MOG in patients with multiple sclerosis, clearly indicates that MOG is probably an important target autoantigen in this disease. Author Affiliation: (1) Neuroimmunology Laboratory, Faculty of Science and Technology, La Trobe University, Bundoora, Melbourne, Victoria, 3083, Australia, AU Article note: Received: 6 June 1996 / Accepted: 20 August 1996