A NEUTRALIZING EPITOPE OF THE SUPERANTIGEN SEA HAS AGONIST ACTIVITY ON T-CELLS

We have previously shown that sequence 121-149 of the staphylococcal e nterotoxin superantigen SEA plays an important role in superantigen fu nction. A synthetic peptide of this region, SEA(121-149), blocks SEA b inding to class II MHC molecules and induces interleukin-1 and tumor n ecrosis factor production in monocytes. In this study, we further emph asize the structural and functional significance of this region of SEA by showing that the SEA(121-149) peptide induces T cell proliferation in a manner similar to that of SEA. SEA(121-149) reacted with antibod ies produced to SEA, and the SEA(121-149) specific antibodies neutrali zed SEA mitogenic activity. A tetrameric form of SEA(121-149) showed i ncreased binding to antibodies and enhanced T cell activation, consist ent with the greater avidity associated with increased valency. These data suggest that the internal domain of SEA corresponding to residues 121-149 plays an important role in superantigen activity. (C) 1996 Ac ademic Press, Inc.