Identification of capsid epitopes of Theiler's virus recognized by CNS-infiltrating CD4+ T cells from virus-infected C57BL/6 mice

Intracerebral infection of Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease in some mouse strains but not in others. We report here for the first time two new predominant capsid epitopes (VP421-40 and VP2201-220) recognized by CD4+ T cells from virus-infected resistant C57BL/6 mice based on IFNγ ELISPOT assay utilizing a 20-mer peptide library covering the entire capsid proteins. Further experiments by IFNγ ELISPOT and flow cytometry for intracellular IFNγ production using truncated peptides indicated that the epitope regions recognized by CNS-infiltrating CD4+ T cells are VP425-38 and VP2206-220, respectively. No apparent reduction in the T cell response to these viral epitopes is seen in the CNS of IL-12- and ICAM-1-deficient C57BL/6 mice compared to those in control C57BL/6 mice, suggesting that T cell response to TMEV in the CNS is largely insensitive to the absence of these proinflammatory cytokine and adhesion molecules. Therefore, these newly defined CD4+ T cell epitopes are likely to provide an important tool to investigate the role of CD4+ T cell responses in H-2b-bearing congenic strains.