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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.

Type

Journal article

Journal

Int Immunol

Publication Date

07/1995

Volume

7

Pages

1057 - 1063

Keywords

Amino Acid Sequence, Bacterial Toxins, Base Sequence, Cell Line, Clonal Anergy, Dose-Response Relationship, Immunologic, Enterotoxins, Epitopes, Humans, Immune Tolerance, Lymphocyte Activation, Molecular Sequence Data, Peptide Fragments, Receptor-CD3 Complex, Antigen, T-Cell, Staphylococcus aureus, Superantigens, T-Lymphocytes, Tetanus Toxin