Role of individual T-cell epitopes of Theiler's virus in the pathogenesis of demyelination correlates with the ability to induce a Th1 response

Robert L. Yauch, Joann P. Palma, Hiroyuki Yahikozawa, Chang Sung Koh, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. Three major T-cell epitopes have previously been identified within the VP1 (VP1233-250), VP2 (VP274-86), and VP3 (VP324- 37) capsid proteins in virus-infected SJL/J mice. These epitopes appear to account for the majority (-90%) of major histocompatibility complex class II- restricted T-cell responses to TMEV. Interestingly, the effect of immunization with synthetic peptides bearing the predominant T-cell epitopes on the course of TMEV-induced demyelination indicates that T cells reactive to the VP1 and VP2 epitopes, but not VP3, accelerate the pathogenesis of demyelination. The predominant pathogenic role of the T cells is verified by similar immunization with the fusion proteins containing the entire individual capsid proteins. The order of appearance and level of T cells specific for the individual epitopes during the course of demyelination are similar to each other. However, cytokine profiles of T cells from virus- infected mice indicate that T cells specific for the VP1 (and perhaps the vP2) epitope are Th1, whereas T cells reactive to VP3 are primarily Th2. These results suggest that Th1-type cells specific for VP1 and VP2 are involved in the pathogenesis of vital demyelination induced by TMEV. Thus, a predominance of Th1-inducing viral epitopes is likely critical for the pathogenesis of demyelination.

Original languageEnglish (US)
Pages (from-to)6169-6174
Number of pages6
JournalJournal of virology
Volume72
Issue number7
DOIs
StatePublished - Jul 1998

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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