Mutations defining functional regions of the superantigen staphylococcal enterotoxin B.
Staphylococcal enterotoxin B (SEB) is both a superantigen and toxin. As a superantigen, SEB can bind to major histocompatibility complex (MHC) class II molecules to form a ligand for alpha/beta T cell receptors bearing particular V beta elements. As a toxin, SEB causes rapid weight loss in mice sometimes leading to death. We show here that both of these functions map to the NH2-terminal portion of the toxin. Three regions were identified: one important in MHC class II binding, one in T cell recognition, and one in both functions. These results support the conclusion that the toxicity of SEB is related to massive T cell stimulation and release of cytokine mediators and show that the residues interacting with MHC and the T cell receptor are intertwined.
Kappler
J W
JW
Howard Hughes Medical Institute, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80207.
Herman
A
A
Clements
J
J
Marrack
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000235:genetics* / Q000276:immunology / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D012689:Sequence Homology, Nucleic Acid; D013211:Staphylococcus aureus / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D015431:Weight Loss / Q000187:drug effects
D000911:Antibodies, Monoclonal; D004269:DNA, Bacterial; D004768:Enterotoxins; D000939:Epitopes; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C031818:enterotoxin B, staphylococcal