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 Vβ genes

H. Offner, M. Vainiene, D. P. Gold, B. Celnik, R. Wang, G. A. Hashim, A. A. Vandenbark

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Abstract

In Lewis rats, immunization with myelin 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 Vβ8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR Vβ 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 Vβ8 (46%+) and Vβ6 (31%+), however, SC clones were strongly biased (86%+) in their expression of Vβ6. This V gene bias raised the possibility of TCR peptide therapy using Vβ6 peptides. The Vβ6 sequence was similar to Vβ8.2 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 Vβ6+ and Vβ8+ T cells, or guinea pig basic protein, biased only in Vβ8+ 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.

Original languageEnglish (US)
Pages (from-to)1706-1711
Number of pages6
JournalJournal of Immunology
Volume148
Issue number6
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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