Sj. Gerety et al., CLASS-II-RESTRICTED T-CELL RESPONSES IN THEILERS MURINE ENCEPHALOMYELITIS VIRUS-INDUCED DEMYELINATING DISEASE .5. MAPPING OF A DOMINANT IMMUNOPATHOLOGIC VP2 T-CELL EPITOPE IN SUSCEPTIBLE SJL J MICE/, The Journal of immunology, 152(2), 1994, pp. 908-918
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating
disease is a relevant mouse model of multiple sclerosis. Demyelination
is linked to persistent TMEV infection of the central nervous system
and characterized by perivascular inflammatory mononuclear infiltrates
and primary demyelination. Myelin damage is a T cell-dependent proces
s and susceptibility correlates with the temporal development of chron
ic virus-specific delayed-type hypersensitivity (DTH) responses. Our p
revious results have shown that inflammatory processes mediated by Th1
cells specific for a determinant(s) on virus capsid protein 2 (VP2) p
lay a major immunopathologic role in SJL/J mice. This study identifies
a 13 amino acid peptide on VP2 (VP74-86) as the immunodominant T cell
epitope in TMEV-infected and-immunized SJL/J mice, and demonstrates t
he ability of that sequence to prime for the majority of the SJL/J DTH
T cell response to intact TMEV. The importance of T cell responses to
this epitope in the demyelinating process was illustrated by experime
nts in which SJL/J mice displayed an increased incidence and accelerat
ed onset of clinical disease after peripheral immunization with a fusi
on protein containing VP274-84 before intracerebral infection with a s
uboptimal dose of the BeAn strain of TMEV. Identification of this immu
nopathologic TMEV T cell epitope will be critically important for deli
neation of the mechanisms of T cell-mediated myelin damage and for pot
ential use to prevent and/or treat TMEV-induced demyelinating disease
via the induction of epitope-specific tolerance.