RESIDUES NEAR THE AMINO AND CARBOXYL TERMINI OF STAPHYLOCOCCAL-ENTEROTOXIN-E INDEPENDENTLY MEDIATE TCR V-BETA-SPECIFIC INTERACTIONS

Previous studies identified three COOH-terminal residues in staphyloco ccal enterotoxin E (SEE; Asp(200), Pro(206), and Asp(207)) that in par t mediate TCR V beta recognition. We have identified an additional thr ee residues near the NH2 terminus of SEE (Arg(20), Asn(21) and Ser(24) ) that are needed in conjunction with these COOH-terminal residues to fully restore native levels of V beta-specific T cell proliferation, A staphylococcal enterotoxin A (SEA)-SEE hybrid molecule containing the NH2-terminal V beta determinants of SEE alone exhibited VP specificit ies of both SEA and SEE, indicating that these residues of SEE indepen dently contribute to V beta recognition and do not obscure the native V beta determinants of SEA. These findings suggest that the ability of SEE to activate certain V beta-specific T cell subsets may result fro m multiple interactions with a single TCR beta-chain or perhaps by cro ss-linking two TCR. High affinity binding to HLA-DR1, a property of na tive SEA, was not altered in the SEA-SEE hybrid enterotoxins containin g amino acid substitutions in regions 20 to 24 and 200 to 207, indicat ing that residues comprising the V beta determinants of SEE are separa te from residues that contribute to HLA-DR1 binding affinity, Computer models of the predicted structure of SEE revealed that the V beta det erminants of SEE are located on two adjacent solvent-exposed loops. Th us, the residues of SEE that mediate v beta recognition may coalesce t o form a TCR binding site with specificities for multiple TCR beta-cha ins.