Differences in Avidity and Epitope Recognition of CD8+T Cells Infiltrating the Central Nervous Systems of SJL/J Mice Infected with BeAn and DA Strains of Theiler's Murine Encephalomyelitis Virus

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Abstract
Theiler's murine encephalomyelitis virus (TMEV) infection induces immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infectious model for human multiple sclerosis. To investigate the pathogenic mechanisms, two strains of TMEV (DA and BeAn), capable of inducing chronic demyelination in the central nervous system (CNS), have primarily been used. Here, we have compared the T-cell responses induced after infection with DA and BeAn strains in highly susceptible SJL/J mice. CD4+ T-cell responses to known epitopes induced by these two strains were virtually identical. However, the CD8+ T-cell response induced following DA infection in susceptible SJL/J mice was unable to recognize two of three H-2Ks-restricted epitope regions of BeAn, due to single-amino-acid substitutions. Interestingly, T cells specific for the H-2Ks-restricted epitope (VP111-20) recognized by both strains showed a drastic increase in frequency as well as avidity after infection with DA virus. These results strongly suggest that the level and avidity of virus-specific CD8+ T cells infiltrating the CNS could be drastically different after infection with these two strains of TMEV and may differentially influence the pathogenic and/or protective outcome.

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