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.
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 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 biased (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.
Offner
H
H
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97201.
Vainiene
M
M
Gold
D P
DP
Celnik
B
B
Wang
R
R
Hashim
G A
GA
Vandenbark
A A
AA
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007116:Immunization, Passive; D008198:Lymph Nodes / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta