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The Journal of Immunology, 1999, 162: 7049-7057.
Copyright © 1999 by The American Association of Immunologists

Diverse Fine Specificity and Receptor Repertoire of T Cells Reactive to the Major VP1 Epitope (VP1230–250) of Theiler’s Virus: Vß Restriction Correlates with T Cell Recognition of the C-Terminal Residue1

Byung S. Kim2,*, Young Y. Bahk*, Hee-Kap Kang*, Robert L. Yauch3,*, Jeong-Ah Kang*, Mi-Jung Park* and Nicholas M. Ponzio{dagger}

* Departments of Microbiology-Immunology and Pathology, Northwestern University Medical School, Chicago, IL 60611; and {dagger} Department of Laboratory Medicine and Pathology, University of Medicine and Dentistry–New Jersey Medical School, Newark, NJ 07103

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 Vß16. The majority (8/11) of the Vß16+ 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 Vß16. However, the complementarity-determining region 3 sequences of the Vß16+ T cell hybridomas were markedly heterogeneous. In contrast, such a restriction was not found in the V{alpha} usage. Only restricted residues at this C-terminal position allowed for T cell activation, suggesting that Vß16 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 Vß (but not V{alpha}) subfamily-specific sequence, resulting in a highly restricted Vß repertoire of the epitope-specific T cells.




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