Myelin 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 MOG35-55 peptide produces a paralytic relapsing-remitting neurological disease with extensive plaque-like demyelination. The antibody response to MOG35-55 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 MOG37-46, which is contiguous to the dominant T cell epitope contained within MOG44-55. NOD/Lt and C57BL/6 mice were also susceptible to severe neurological disease following injection with recombinant MOG or MOG35-55 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 MOG35-55 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.

Myelin oligodendrocyte glycoprotein (MOG) is postulated to be a target autoantigen in multiple sclerosis (MS). Here we investigated the encephalitogenicity of an immunodominant epitope of MOG, peptide 35-55, in various strains of mice. An MS-like disease was induced in NOD/Lt mice (H-2g7) and C57BL/6 mice (H-2b) by a single injection of MOG35-55 in CFA. The disease followed a relapsing-remitting course in NOD/Lt mice, whereas C57BL/6 mice developed a chronic paralytic disease. Histologically, the disease in both strains was characterized by cellular infiltration and multifocal demyelination in the CNS. Significant DTH type reactions to MOG35-55 were only seen in MOG-susceptible animals, with the NOD/Lt mice showing the strongest responses. Susceptible mice also showed specific antibody responses to MOG35-55 but not to a panel of other MOG peptides. These results provide further evidence for the role of MOG as a highly autoantigenic molecule capable of inducing severe demyelinating disease.

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