Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic
demyelinating disease in the central nervous system characterized by persistent
viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to
demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of
antigen-presenting molecules that confer resistance to
viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for
demyelination, infectious virus, and local virus
antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal
demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local
viral antigen production and
demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the
viral antigen to the immune system, resulting in local virus clearance and absence of subsequent
demyelination.