The myelin-associated oligodendrocytic basic protein (MOBP) as a relevant primary target autoantigen in multiple sclerosis.
Multiple sclerosis (MS) is a disease of the human CNS, characterized by perivascular inflammation, demyelination and axonal damage. Although the etiology of MS is unknown, it is believed that the disease results from destructive autoimmune mechanisms, presumably initiated by abnormal activation of potentially pathogenic autoimmune T-cells recognizing CNS components. The myelin-associated oligodendrocyte basic protein (MOBP), a relatively abundant CNS-specific myelin protein, which plays a role in stabilizing the myelin sheath in the CNS, has recently been implicated in the pathogenesis of MS. Here we review studies showing that MOBP is as an important candidate target antigen in MS as the other widely studied target antigens, myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). The studies summarized below indicate that T-cell autoimmunity against MOBP can be detected in MS patients; T-cells reactive against MOBP can be pathogenic in several mouse strains as well as in the "humanized" HLA-DR15-Tg mice; and, that the HLA-DQ6-restricted, but not HLA-DR15-restricted, MOBP-reactive T-cells cause in HLA-DR15-Tg mice MS-like clinical disease associated with perivascular and parenchymal infiltration, demyelination, axonal loss, and optic neuritis. Accordingly, the MOBP should be considered a bona fide primary target antigen in MS, in addition to MBP, PLP, and MOG.
Kaushansky
Nathali
N
Department of Immunology, The Weizmann Institute of Science, P.O. Box 26, Rehovot 76000, Israel.
Eisenstein
Miriam
M
Zilkha-Falb
Rina
R
Ben-Nun
Avraham
A
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009902:Optic Neuritis; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; C560487:MOBP protein, human; C571326:MOG protein, human; C560488:Mobp protein, mouse; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein