Both alpha-helices along the major histocompatibility complex binding cleft are required for staphylococcal enterotoxin A function.
The superantigen staphylococcal enterotoxin A (SEA) requires interaction with class II major histocompatibility complex (MHC) molecules to activate T cells. We have previously used the synthetic peptide approach to establish one side of the hypothetical class II foreign-antigen binding cleft, alpha-helical region 65-85 of the beta chain, as a binding site involved in accessory cell presentation of SEA to T cells. To further characterize the structural basis for MHC-SEA interaction we have examined the role of the alpha-helical regions of the class II alpha and beta chains in SEA function. Using the synthetic peptide approach, we have found that both alpha-helical regions are required for SEA-induced proliferation. Their corresponding peptides directly bound SEA. Although the beta-chain peptides were able to inhibit SEA binding to human and mouse cells, the alpha-chain peptides were not. The data suggest that the alpha-helices along both sides of the hypothetical class II MHC molecule binding cleft are required for SEA-induced function, whereas the beta-chain alpha-helix is sufficient for SEA binding. A model of superantigen presentation is proposed wherein the MHC beta chain, possibly region 70-80, interacts with SEA region 1-45, whereas another region of SEA binds region 51-80 of the alpha chain.
Russell
J K
JK
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611.
Pontzer
C H
CH
Johnson
H M
HM
D001665:Binding Sites; D003208:Concanavalin A; D004261:DNA Replication / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology*; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D046911:Macromolecular Substances; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D004768:Enterotoxins; D006681:HLA-D Antigens; D046911:Macromolecular Substances; D010455:Peptides; D003208:Concanavalin A; C026066:enterotoxin A, Staphylococcal