Epitope spreading in theiler's murine encephalomyelitis virus (tmev)-induced demyeljnating disease

W. C W Pao*, C. L. Vanderluot, R. L. Yauch, Byung S Kim, Stephen D Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

tt has long been suspected that autoimmune disease \s often preceded by infections with viral agents. Theiler's murine encephalomyelitis virus (TMEV)induced demyelinating disease in mice is a relevant animal model of multiple sclerosis (MS) since both disease are characterized by spastic paralysis, perivascular inflammatory mononuclear infiltrates, and primary demyelination. Earlier experiments have shown that the TMEV-induced demyelinating process is initiated by TMEV-specific CD4Th1 cells which target virus persisting in the CNS. However, our recent experiments indicate that mice with chronic demyelination develop T cell responses (both proliferative and delayed-typed hypersensitivity) to the major immunodominant epitope on myelin proteolipid protein (PLP139-151) 3-4 weeks following the initial appearance of clinical disease, and an immune-mediated response against PLP178-191, PLP56-70 and MOG92-104 by five months post-infection. PLP139-151 -specific responses can also be observed in the CNS. This secondary autoimmune reactivity does not appear to be due to T cell specific molecular mimicry, i.e. cross-reactivity between viral T cell epitopes and epitopes on self myelin proteins, since the PLP epitope shares no sequence homology with TMEV proteins and no crossreactivity at the T cell level between TMEV and encephalitogenic myelin epitopes is noted. Rather, the development of this autoimmune response is likely due to epitope spreading, wherein self-reactive T cells are primed as a result of chronic release of endogenous myelin epitopes. Epitope spreading thus provides a mechanism whereby a chronic virus infection can lead to autoimmune sequelae in the absence of a cross-reactive immune response. (Supported in part by USPHS NIH Grant NS23349).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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