T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis

The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody-mediated demyelination in experimental autoimmune encepha lomyelitis (EAE) resulted in the re-evaluation of the role of B cell respon ses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central nervous system specific myelin glycoprotein that is expre ssed preferentially on the outermost surface of the myelin sheath. Although MOG is only a minor component of CNS myelin it is highly immunogenic, indu cing severe EAE in both rodents and primates. In rat and marmoset models of MOG-induced EAE demyelination is antibody-dependent and reproduces the imm unopathology seen in many cases of MS. In contrast, in mice inflammation in the CNS can result in demyelination in the absence of a MOG-specific B cel l response, although if present this will enhance disease severity and demy elination. Clinical studies indicate that autoimmune responses to MOG are e nhanced in many CNS diseases and implicate MOG-specific B cell responses in the immunopathogenesis of multiple sclerosis. This review provides a summa ry of our current understanding of MOG as a target autoantigen in EAE and M S, and addresses the crucial question as to how immune tolerance to MOG may be maintained in the healthy individual. (C) 2001 Wiley-Liss, Inc.