title: The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode of action.
abstract: Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen that stimulates Vbeta2-bearing human T cells, but is inactive in mice. SPE-C binds with high affinity to both human HLA-DR and murine I-E molecules, but not to murine I-A molecules in a zinc-dependent fashion. Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatibility complex (MHC) class II alpha-chain binding site common to all other bacterial superantigens. Despite this, SPE-C cross-links MHC class II to induce homotypic aggregation of class II-bearing B cells. Nondenaturing sodium dodecyl sulfate electrophoresis and size exclusion chromatography revealed that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or alkaline pH. These data support a recent crystal structure of SPE-C and reveal yet another mechanism by which bacterial superantigens ligate and cross-link MHC class II.
authors.affiliation: Department of Molecular Medicine, University of Auckland, 92019 Auckland, New Zealand.
authors.forename: P L
authors.initials: PL
authors.lastname: Li
authors.forename: R E
authors.initials: RE
authors.lastname: Tiedemann
authors.forename: S L
authors.initials: SL
authors.lastname: Moffat
authors.forename: J D
authors.initials: JD
authors.lastname: Fraser
mesh_terms: D001426:Bacterial Proteins; D002460:Cell Line; D018360:Crystallography, X-Ray; D019281:Dimerization; D005098:Exotoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins; D011485:Protein Binding / Q000276:immunology; D011749:Pyrogens / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000276:immunology*; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D011749:Pyrogens; D011994:Recombinant Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; D015032:Zinc