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).
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.
Yauch
R L
RL
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Kim
B S
BS
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D016207:Cytokines / Q000032:analysis; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology; D000939:Epitopes / Q000276:immunology; D007201:Indicator Dilution Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D011051:Poliomyelitis / Q000276:immunology* / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology*
D000956:Antigens, Viral; D036022:Capsid Proteins; D016207:Cytokines; D000939:Epitopes; D011993:Recombinant Fusion Proteins; C442551:VP1 protein, Theilovirus