A predominant viral epitope recognized by T cells from the periphery and demyelinating lesions of SJL/J mice infected with Theiler's virus is located within VP1233-244

Robert L. Yauch, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible strains of mice results in a chronic, immune-mediated demyelinating disease that shares many features with human multiple sclerosis. As with human MS, T lymphocytes seem to be critically important for the pathogenesis of this virally induced, demyelinating disease. Therefore, determining the fine specificity of the T cell response may be essential for elucidating the mechanism(s) involved in demyelination. By using fusion proteins and synthetic peptides, we have initially identified a region within the amino acid residues 233 to 250 of the VP1 capsid protein of Theiler's virus that is recognized by T cells from either TMEV-immunized or TMEV-infected, demyelination-susceptible SJL/J mice. A T lymphocyte precursor frequency analysis indicates that a major TMEV-reactive T cell population in the periphery of virus-infected mice recognizes this VP1 region. The fine epitope specificity has been further determined to be within VP1-233- 244 using additional synthetic peptides. VP1-233-244-specific T cells seem to represent a significant population of TMEV-reactive T lymphocytes within the demyelinating lesions, because such T cells have been cloned from the spinal cords of infected mice. Interestingly, all TMEV- specific T cell clones derived from the demyelinating lesions, regardless of epitope specificity, produce IFN-γ on stimulation and thus may play a critical role in the recruitment and activation of inflammatory cells leading to demyelination. Taken together, these data suggest that a T cell response against VP1-233-244 is involved in the pathogenesis of TMEV-induced demyelinating disease.

Original languageEnglish (US)
Pages (from-to)4508-4519
Number of pages12
JournalJournal of Immunology
Volume153
Issue number10
StatePublished - 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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