CD8(-CELL EPITOPES WITHIN THE SURFACE GLYCOPROTEIN OF A NEUROTROPIC CORONAVIRUS AND CORRELATION WITH PATHOGENICITY() T)

CD8(+) T cells with cytotoxic activity against the surface glycoprotei n (S) of mouse hepatitis virus, strain JHM, have been identified in th e central nervous system (CNS) of both acutely and chronically infecte d C57BL/6 mice. In this report, two specific epitopes recognized by th ese CNS-derived cells were identified, using a panel of peptides chose n because they conformed to the allele-specific binding motif for MHC class I H-2K(b) and H-2D(b). The active peptides encompassed residues 510 to 518 (CSLWNGPHL, H-2D(b)) and 598 to 605 (RCQIFANI, H-2K(b)). Bo th epitopes are located within the region of the S protein previously shown to be prone to deletion after passage in animals, These deleted strains are generally less neurovirulent than the wild-type virus but still are able to cause demyelination. Since C57BL/6 mice become persi stently infected more commonly than many other strains of mice, these data are consistent with a role for CD8(+) T-cell escape mutants in th e pathogenesis of the demyelinating disease. This is the first report of CD8(+) T-cell epitope Localization within the S protein, the protei n most strongly implicated thus far in pathogenesis in the host.