Multiple binding sites on the superantigen, staphylococcal enterotoxin B, imparts versatility in binding to MHC class II molecules.
To determine MHC class II molecule binding regions of staphylococcal enterotoxin B (SEB), we employed a structurally based approach in which eight overlapping peptides of the entire SEB molecule were synthesized to encompass discrete secondary structures based on the SEB crystalline structure. SEB peptides encompassing amino acid residues 1-33, 31-64 and 179-212 successfully competed with [125I]SEB for binding to DR1 transfected L cells. In contrast, SEB peptides encompassing amino acid residues 1-33, 124-154, 150-183 and 179-212 successfully competed with [125I]SEB for binding to Raji cells (HLA-DR3, DRw10, DQw1 and DQw2). In addition, the SEB peptide (124-154) inhibited the mitogenic function of SEB. Thus, we have identified multiple regions, including the C-terminus, of SEB that are involved in binding to MHC class II and have shown that these interactions are complex and dependent on the haplotype of the MHC class II molecule.
Soos
J M
JM
Department of Microbiology, University of Florida, Gainesville 32611.
Johnson
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes; D001665:Binding Sites; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004768:Enterotoxins / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007739:L Cells; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000378:metabolism; D018089:Superantigens / Q000737:chemistry / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D004768:Enterotoxins; D006684:HLA-DR Antigens; D010455:Peptides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D013936:Thymidine