T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A

We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T-cell antigen receptor β chain variable region Vβ3. SEA is known to stimulate murine T cells bearing certain Vβ elements, among them Vβ3. Five peptides were synthesized representing amino acids 1-24, 20-44, 39-60, 57-77, and 74-95 of Vβ3. We demonstrate here that soluble Vβ3-bearing β chains can bind to a complex of SEA and major histocompatibility complex class II and that the synthetic peptide Vβ3-(57-77) blocked this interaction. The peptide Vβ3-(57-77) also inhibited SEA-induced interferon-γ production and SEA-induced proliferation of B10.BR spleen cells. Conversely, the peptide corresponding to amino acids 57-77 of Vβ8.2, a Vβ element that is not recognized by SEA, decreased staphylococcal enterotoxin C-2-induced proliferation but did not affect SEA-induced proliferation. The peptide inhibition of SEA-induced function was due at least in part to inhibition of Vβ3-bearing T-cell activity, since the percentage of T cells reactive with an anti-Vβ3 monoclonal antibody was significantly reduced by Vβ3-(57-77). These data suggest that the region of Vβ3 encompassing amino acids 57-77 is an area that displays the appropriate sequence and conformation for binding of the SEA molecule and blocking of the resultant interaction with the T-cell antigen receptor.