MYELIN OLIGODENDROCYTE GLYCOPROTEIN - A NOVEL CANDIDATE AUTOANTIGEN IN MULTIPLE-SCLEROSIS

Myelin oligodendrocyte glycoprotein (MOG) is a member of the immunoglo bulin superfamily expressed exclusively in central nervous system (CNS ) myelin. While the function of MOG is unknown, a number of studies ha ve shown that immune responses to MOG contribute to the autoimmune-med iated demyelination seen in animals immunized with whole CNS tissue. T his paper summarizes our recent studies, which unequivocally demonstra te that MOG by itself is able to generate both an encephalitogenic T c ell response and an autoantibody response in Lewis rats and in several strains of mice. In Lewis rats the injection of both native MOG and M OG(35-55) peptide produces a paralytic relapsing-remitting neurologica l disease with extensive plaque-like demyelination. The antibody respo nse to MOG(35-55) was highly restricted, as no reactivity to either ot her MOG peptides or myelin proteins could be detected. Fine epitope ma pping showed that antibody from serum and cerebrospinal fluid of injec ted rats reacted strongly to MOG(37-46), which is contiguous to the do minant T cell epitope contained within MOG(44-55). NOD/Lt and C57BL/6 mice were also susceptible to severe neurological disease following in jection with recombinant MOG or MOG(35-55) peptide, indicating that th is specific CNS autoantigen, or some of its determinants, can induce a pathogenic response across animal species. Severe paralysis and exten sive demyelination were seen in both strains, but NOD/Lt mice experien ced a chronic relapsing disease whereas C57BL/6 mice had a chronic non -remitting disease. Moreover, transfer of MOG(35-55) T cells into naiv e 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 de velopment of severe demyelinating disease. This, together with our dem onstration that there is a predominant T cell response to MOG in patie nts with multiple sclerosis, clearly indicates that MOG is probably an important target autoantigen in this disease.