The Journal of Immunology, Vol 153, Issue 10 4508-4519, Copyright © 1994 by American Association of Immunologists

ARTICLES

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 VP1(233-244)

RL Yauch and BS Kim
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.

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- gamma 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.

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