MHC HAPLOTYPE-DEPENDENT REGULATION OF MOG-INDUCED EAE IN RATS

Experimental autoimmune encephalomyelitis (EAE) induced in the rat by active immunization with myelin-oligodendrocyte-glycoprotein (MOG) is mediated by synergy between MOG-specific T cells and demyelinating MOG -specific antibody responses. The resulting disease is chronic and dis plays demyelinating central nervous system (CNS) pathology that closel y resembles multiple sclerosis. We analyzed major histocompatibility c omplex (MHC) haplotype influences on this disease. The MHC haplotype d oes not exert an all-or-none effect on disease susceptibility. Rather, it determines the degree of disease susceptibility, recruitment of MO G-specific immunocompetent cells, clinical course, and CNS pathology i n a hierarchical and allele-specific manner. Major haplotype-specific effects on MOG-EAE map to the MHC class II gene region, but this effec t is modified by other MHC genes. In addition, non-MHC genes directly influence both disease and T cell functions, such as the secretion of IFN-gamma. Thus, in MOG-EAE, allelic MHC class II effects are graded, strongly modified by other MHC genes, and overcome by effects of non-M HC genes and environment.