Roles of the H-2D(b) and H-K(b) genes in resistance to persistent Theiler's murine encephalomyelitis virus infection of the central nervous system

Abstract

Theiler's murine encephalomyelitis virus, a member of the Picornaviridae family, persists in the spinal cord of susceptible strains of mice. Resistant strains of mice, such as the H-2(b) strain, clear the virus infection after an acute encephalomyelitis. The H-2D locus, but not the H-2K locus, has a major effect on this resistance, although both loci code for MHC class I molecules with similar general properties. For the present work, we rendered susceptible H-2(q) FVB/N mice transgenic for either the H-2D(b)gene, the H-2K(b) gene or a chimeric H-2D(b)/K(b) gene in which the exons encoding the peptide-binding groove of the H-2K(b) gene have been replaced by those of the H-2D(b)gene. Mice transgenic for either the H-2D(b)gene or the chimeric H-2D(b)/K(b) gene were significantly more resistant to persistent virus infection than mice transgenic for the H-2K(b) gene, suggesting that the difference in the effects of the H-2D(b)gene and the H-2K(b) gene are due to the nature of the peptides presented by these class I molecules.