Clearance of Theiler's virus infection depends on the ability to generate a CD8⁺ T cell response against a single immunodominant viral peptide

Theiler's murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease in the central nervous system of susceptible mice. Resistance to persistent TMEV infection maps to the D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response. Introduction of the D^b gene into the FVB strain confers resistance to this otherwise susceptible mouse line. Infection of the FVB/D^b mouse with TMEV provides a model where antiviral resistance is determined by a response elicited by a single class I molecule. Resistant mice of the H-2^b haplotype mount a vigorous H-2D^b-restricted immunodominant response to the VP2 capsid protein. To investigate the xtent of the contribution of the immunodominant T cell population in resistance to TMEV, FVB/D^b mice were depleted of VP2-specific CD8⁺ T cells by peptide treatment prior to virus infection. Peptide-treated mice were not able to clear the virus and developed extensive demyelination. These findings demonstrate that the D^b-restricted CD8⁺ T cells specific for a single viral peptide can confer resistance to TMEV infection. Our ability to manipulate this cellular response provides a model for investigating the mechanisms mediating protection against virus infection by CD8⁺ T cells.