Agonist properties of a microbial superantigen peptide

Staphylococcal enterotoxin A (SEA) binds to class II major histocompatibility complex (MHC) molecules and stimulates monocytes to produce tumor necrosis factor alpha (TNF alpha) and interleukin one (IL-1). We have examined the monocyte stimulatory activity of individual synthetic peptides encompassing the entire sequence of the SEA molecule. Only one peptide, SEA(121-149), induced both TNF alpha and IL-1 production at a concentration as low as 30 microM. Consistent with its effects on monocyte function, SEA(121-149) was shown to bind directly to class II MHC molecules on the surface of both monocytes and B cells, and its binding was inhibited specifically by native SEA. Further, polyclonal antibody to SEA(121-149) inhibited induction of TNF alpha by both SEA and toxic shock syndrome toxin one. Thus, we have identified SEA(121-149) as a peptide agonist of SEA monocyte stimulatory activity.