H-2D(b-/-) mice are susceptible to persistent infection by Theiler's virus

H-2(b) mice are resistant to persistent infection of the central nervous sy stem by Theiler's virus. They clear the infection 7 to 10 days after intrac ranial inoculation. Resistance maps to the H-2D gene and not to the H-2K ge ne and is associated with a potent antiviral cytotoxic T-lymphocyte (CTL) r esponse. We used H-2(b) mice in which the H-2D or the H-2K gene had been in activated to dissect the respective roles of these genes in resistance. We report that H-2D(-/-) but not H-2K(-/-) mice were susceptible to persistent infection. Furthermore, whereas H-2K(-/-) mice mounted a vigorous virus sp ecific CTL response, similar to that of control C57BL/6 mice, the CTL respo nse of H-2D(-/-) mice was nil or minimal. Using target cells transfected wi th the H-2D(b) or the H-2K(b) gene, we showed that the H-2K-restricted CTL response against the virus was minimal in H-2D(-/-) mice. These results dem onstrate that the H-2D(b) and H-2K(b) genes play nonredundant roles in the resistance to this persistent infection.