Theiler's murine encephalomyelitis virus induces chronic demyelinating disease in genetically susceptible mice. The histopathological and immunological manifestation of the disease closely resembles human multiple sclerosis, and, thus, this system serves as a relevant infectious model for multiple sclerosis. The pathogenesis of demyelination appears to be mediated by the inflammatory Th1 response to viral epitopes. In this study, T cell repertoire reactive to the major pathogenic VP1 epitope region (VP1233- 250) was analyzed. Diverse minimal T cell epitopes were found within this region, and yet close to 50% of the VP1-reactive T cell hybridomas used Vβ16. The majority (8/11) of the Vβ16+ T cells required the C-terminal amino acid residue on the epitope, valine at position 245, and every T cell hybridoma recognizing this C-terminal residue expressed Vβ16. However, the complementarity-determining region 3 sequences of the Vβ16+ T cell hybridomas were markedly heterogeneous. In contrast, such a restriction was not found in the Vα usage. Only restricted residues at this C-terminal position allowed for T cell activation, suggesting that Vβ16 may recognize this terminal residue. Further functional competition analysis for TCR and MHC class II-contacting residues indicate that many different residues can be involved in the class II and/or TCR binding depending on the T cell population, even if they recognize the identical minimal epitope region. Thus, recognition of the C-terminal residue of a minimal T cell epitope may associate with a particular Vβ (but not Vα) subfamily-specific sequence, resulting in a highly restricted Vβ repertoire of the epitope-specific T cells.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - Jun 15 1999|
ASJC Scopus subject areas
- Immunology and Allergy