Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes
Offner, H.; Vainiene, M.; Gold, D.P.; Celnik, B.; Wang, R.; Hashim, G.A.; Vandenbark, A.A.
Journal of Immunology 148(6): 1706-1711
1992
ISSN/ISBN: 0022-1767 PMID: 1371785 Document Number: 397800
In Lewis rats, immunization with meylin basic protein induces two distinct encephalitogenic T cell populations, those responding to the immunodominant 72-89 epitope and those specific for a secondary epitope including residues 87-99. The 72-89 specific T cells were I-A restricted and preferentially expressed V.beta.8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR V.beta. gene use in T cells reactive to the secondary epitope, we characterized 23 T cell clones from the lymph nodes (LN) and spinal cords (SC) of rats immunized with either whole basic protein or synthetic peptides S85-99 and S87-99 that were found to be functionally similar. The S85-99/S87-99 specific clones from LN and SC were all encephalitogenic despite differences in recognition of intact basic protein and class II MHC restriction. Unlike LN clones that overexpressed V.beta.8 (46%+) and V.beta.6 (31%+), however, SC clones were strongly based (86%+) in their expression of V.beta.6. This V gene bias raised the possibility of TCR peptide therapy using V.beta.6 peptides. The V.beta.6 sequence was similar to V.beta.8.2 in the CDR2 region, and the corresponding peptides from this region were found to be cross-reactive in vivo. Moreover, both peptides were effective in the treatment of EAE induced with either S85-99, biased in V.beta.6+ and V.beta.8+ T cells, or guinea pig basic protein, biased only in V.beta.8+ T cells. These data demonstrate the presence of common immunogenic epitopes among subsets of TCR V region gene families that possess important regulatory activity on effector T cell function.