Comparison of peptide and superantigen-induced anergy in a peptide-specific polyclonal human T cell line.
T cells recognizing tetanus toxin peptide 'p2' (sequence 830-844) raised in HLA DR6 individuals preferentially express V beta 2 in the TCR. A p2-specific T cell line (60% V beta 2+) was used to compare peptide and superantigen [toxic shock syndrome toxin-1 (TSST-1)]-induced clonal anergy. Many experiments consistently revealed that the degree of 'tolerance' or 'clonal anergy' induced by peptide was greater than with the superantigen TSST-1. These results are of interest in a number of contexts. First they suggest that using superantigens or anti-V beta to delete the majority population of T cells may not be sufficient to diminish an autoimmune response. Secondly, the results indicate that induction of anergy of a large proportion of peptide-specific T cells does not lead to a suppressive bystander effect on the remaining responsive T cells. These results emphasize the need to define the dominant autoantigenic epitopes in human autoimmune diseases, since peptide based therapy such as the use of peptide analogues to induce anergy or a change in cytokine profile, is possibly more effective in controlling undesired immune responses than the use of non-antigen, TCR-directed approaches such as superantigens.
Kennedy Institute of Rheumatology, Sunley Division, Hammersmith, London, UK.
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Chu
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Quaratino
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Feldmann
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Londei
D000595:Amino Acid Sequence; D001427:Bacterial Toxins; D001483:Base Sequence; D002460:Cell Line; D017635:Clonal Anergy; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology; D000939:Epitopes; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D018089:Superantigens; D013744:Tetanus Toxin; C030107:enterotoxin F, Staphylococcal