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) rais ed 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 peptid e and superantigen [toxic shock syndrome toxin-1 (TSST-1)]-induced clo nal anergy. Many experiments consistently revealed that the degree of 'tolerance' or 'clonal anergy' induced by peptide was greater than wit h the superantigen TSST-1, These results are of interest in a number o f 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 respo nsive T cells. These results emphasize the need to define the dominant autoantigenic epitopes in human autoimmune diseases, since peptide ba sed 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.