Localization of an immunologically functional region of the streptococcal superantigen pepsin-extracted fragment of type 5 M protein.

Ten overlapping synthetic peptides, spanning the entire amino acid sequence of pepsin-extracted type 5 M protein, (pep M5), were used to delineate regions within this molecule that are important for the mitogenic activity of this streptococcal superantigen. Two of the overlapping peptides, SM5-8 and SM5-10, blocked the response of T cells to pep M5 in a dose-dependent manner. Neither peptide was toxic to T cells, but SM5-8 exhibited nonspecific inhibition of the T-cell response to either superantigen or polyclonal mitogens. In contrast, the inhibition by SM5-10 was pep M5-specific. Analysis of TCR V beta gene usage of the pep M5 response in the presence and absence of SM5-10 revealed that this peptide preferentially blocks the expansion of pep M5-specific V beta elements. The degree of inhibition of V beta expansion varied from one individual to the other, reflecting their TCR repertoire. SM5-10 did not significantly inhibit the response of T cells to other streptococcal superantigens. The data suggest that the region represented by SM5-10 of the pep M5 is important for superantigenic activity. In addition, the ability of this synthetic peptide to inhibit the response to pep M5 provides evidence that the mitogenic response is indeed mediated by this superantigen and is not a result of contamination with other streptococcal superantigens.