Cross-linking of MHC class II molecules by staphylococcal enterotoxin A is essential for antigen-presenting cell and T cell activation.
Two binding sites for MHC class II have previously been identified on opposite sides of the superantigen, staphylococcal enterotoxin A (SEA). The sites mediate separate binding reactions with nonoverlapping regions of class II, and in solution cause SEA to complex with purified HLA-DR1 to form DR1.SEA2 trimers. Here, a set of complementary SEA class II-binding mutants was used to study the interaction of SEA with cell surface MHC class II. The results indicate that both class II binding sites are required on the same toxin molecule for maximal activity, demonstrating that simultaneous ligation of two MHC class II molecules on APCs by a single SEA is essential for effective superantigen function. Coalescence of MHC class II by SEA results in protein tyrosine kinase activation and contributes to the induction of cell:cell adhesion, pro-inflammatory cytokine gene transcription, and T cell proliferation.
Tiedemann
R E
RE
Department of Molecular Medicine, University of Auckland School of Medicine, New Zealand.
Fraser
J D
JD
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D007152:Immunologic Capping; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008213:Lymphocyte Activation; D016297:Mutagenesis, Site-Directed; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology; D018089:Superantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000942:Antigens, Bacterial; D004768:Enterotoxins; D015798:HLA-DR1 Antigen; D007375:Interleukin-1; D011993:Recombinant Fusion Proteins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D006639:Histidine