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 staphylococcal enterotoxin E (SEE; Asp200, Pro206, and Asp207) that in part mediate TCR V beta recognition. We have identified an additional three residues near the NH2-terminus of SEE (Arg20, Asn21, and Ser24 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 to activate alone exhibited V beta specificities of both SEA and SEE, indicating that these residues of SEE independently 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 from multiple interactions with a single TCR beta-chain or perhaps by cross-linking two TCR. High affinity binding to HLA-DR1, a property of native SEA, was not altered in the SEA-SEE hybrid enterotoxins containing amino acid substitutions in regions 20 to 24 and 200 to 207, indicating that residues comprising the V beta determinants of SEE are separate from residues that contribute to HLA-DR1 binding affinity. Computer models of the predicted structure of SEE revealed that the V beta determinants of SEE are located on two adjacent solvent-exposed loops. Thus, the residues of SEE that mediate V beta recognition may coalesce to form a TCR binding site with specificities for multiple TCR beta-chains.
Lamphear
J G
JG
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Mollick
J A
JA
Reda
K B
KB
Rich
R R
RR
D000409:Alanine / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology*; D000818:Animals; D001120:Arginine / Q000276:immunology; D001216:Asparagine / Q000276:immunology; D004768:Enterotoxins / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism*; D012694:Serine / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000737:chemistry* / Q000276:immunology
D000596:Amino Acids; D004768:Enterotoxins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C049463:enterotoxin E, Staphylococcal; C026066:enterotoxin A, Staphylococcal; D012694:Serine; D001216:Asparagine; D001120:Arginine; D000409:Alanine