First, susceptibility vs. resistance to viral persistance and demyelination maps to the D region molecule of the class I gene (Rodriguez et al., 1986) . Second, class I genes are upregulated in neurons, astrocytes, and oligodendrocytes immediately after infection (Redwine et al., 2001) . Third, the upregulation of class I MHC is differentially regulated such that both K and D region molecules are upregulated during the acute phase of the infection, but only D region molecules are upregulated during the chronic demyelinating disease (Altintas et al., 1993) . Fourth, cytotoxic T-cell-mediated killing can be demonstrated for T-cells isolated directly from the infected CNS without in vitro stimulation (Lin et al., 1995) . Fifth, cytotoxic T-cell-mediated killing is directed against the viral capsid proteins of Theiler's virus, primarily VP2, and to a lesser extent VP1 (Lin et al., 1995) . Sixth, in mice of the H-2 b haplotype, VP2 121-130 is the immunodominant peptide recognized specifically within the context of the H-2D b molecule (Borson et al., 1997) . Seventh, FACS using fluorescently labeled tetramers of VP2 121-130 /D b demonstrate that 60% to 80% of all CD8 + T-cells in the CNS of infected mice are directed against this one immunodominant peptide (Johnson et al., 1999) . Eighth, we have shown that mice with a dysfunctional MHC class I induced by genetic deletion of β2microglobulin exhibit profound demyelination of the spinal cord despite normal neurological function (Rivera-Quinones et al., 1998) . Preservation of physiological function was likely due to preservation of axons, and, in fact, we showed that axons upregulated and redistributed sodium channels along demyelinated segments.