DIFFERENTIAL GENERATION OF CLASS-I H-2D-VERSUS H-2K-RESTRICTED CYTOTOXICITY AGAINST A DEMYELINATING VIRUS FOLLOWING CENTRAL-NERVOUS-SYSTEM INFECTION

Despite the fact that both H-2K and D molecules are up-regulated in th e central nervous system (CNS) following Theiler's murine encephalomye litis virus (TMEV) infection, resistance in this virus model of multip le sclerosis maps exclusively to D. To address this paradox, we examin ed the ability of the K and D molecules to present viral antigens to c ytotoxic T lymphocytes (CTL). Whereas no virus-specific CTL were detec ted in the CNS of susceptible B10.Q and B10.S mice 7 days post-infecti on, D-restricted CTL were identified readily in the CNS of resistant B 10 animals. There was no evidence of K-restricted CTL in the CNS of B1 0 mice at day 7 post-infection. The presence of both K- and D-restrict ed virus-specific CTL in the spleen of immunized B10 mice demonstrates that the exclusive use of D molecules by CTL in the CNS of mice 7 day s postinfection is not due to the inability of the K molecules to pres ent viral peptides to lymphocytes. We conclude that the prominent role of the D locus in determining resistance or susceptibility to TMEV-in duced demyelination is determined by factors governing the regulation of the immune response, and not by the presence or absence of CTL prec ursors capable of recognizing viral peptides presented by the K and D antigen-presenting molecules, or by differences in the ability of the K and D molecules to present viral peptides.