Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. T cells play an important role in this immune-mediated disease. We have previously identified two major T cell epitopes within the VP1 (VP1233.250) and VP3 (VP32t37) capsid proteins, based on the reactivities of T cell clones derived from demyelinating spinal cords of virus-infected SJL/J mice. Together with the previously identified VP2 (VP27t) epitope, these three T cell epitopes account for the majority of MHC class ll-restricted T cell responses to TMEV. T cells responsive to the individual epitopes appeared at similar time points during the course of TMEV-induced demyelination. However, peptide-priming experiments indicate that immunization with VP1 and VP2, but not VP3, accelerates the pathogenesis. Further cytokine profiles of T cells from virus-infected mice upon stimulation with individual epitope-peptides in vitro indicate that VP1 and VP2 peptides elicit Th1 cytokines whereas VP3 induces only Th2 cytokines. In contrast, a low-pathogenic variant virus containing a single amino acid substitution in the VP1 epitope resulted in Th2 response. These results strongly suggest that the Th1-type T cells specific for VP1 and VP2 are involved in the pathogenesis of viral demyelination induced by TMEV.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology