Common sequence on distinct V beta genes defines a protective idiotope in experimental encephalomyelitis.
Synthetic TCR peptides expressed by encephalitogenic T cells can induce both cellular and humoral responses that protect against experimental encephalomyelitis. In the Lewis rat, encephalitogenic T cells predominantly express V beta 8.2, and a peptide in the CDR2 region representing residues 39-59 could both protect against and treat experimental autoimmune encephalitis (EAE). Similarly, the homologous and cross reactive 39-59 peptide from V beta 8.6 expressed by an EAE-protective clone also had protective and therapeutic activity against EAE. The consensus sequence between the V beta 8.2 and V beta 8.6 peptides, which included residues 44-54, was postulated to contain the protective idiotope. In this report, we demonstrate that this peptide, designated V beta 8-44-54, has comparable activity to the longer peptides for treating both active and passive EAE. Similar to the longer V beta 8.2-39-59 peptide, the V beta 8-44-54 peptide stimulates protective TCR peptide-specific CD4+, CD8dim T cells restricted by MHC I. We also report for the first time the recovery of V beta 8-44-54 reactive T cells that express a variety of V beta genes in their T-cell receptor (TCR), including V beta 4, 8, 10, 12, 15, 17, 19, and 20. Taken together, these data establish that the V beta 8-44-54 sequence constitutes an important autoregulatory idiotope in EAE.(ABSTRACT TRUNCATED AT 250 WORDS)
Vainiene
M
M
Veterans Affairs Medical Center, Portland, Oregon 97201.
Gold
D P
DP
Celnik
B
B
Hashim
G A
GA
Vandenbark
A A
AA
Offner
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D004247:DNA / Q000032:analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005784:Gene Amplification; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008969:Molecular Sequence Data; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007130:Immunoglobulin Idiotypes; D004247:DNA