title: CD28: direct and critical receptor for superantigen toxins.
abstract: Every adaptive immune response requires costimulation through the B7/CD28 axis, with CD28 on T-cells functioning as principal costimulatory receptor. Staphylococcal and streptococcal superantigen toxins hyperstimulate the T-cell-mediated immune response by orders of magnitude, inducing a lethal cytokine storm. We show that to elicit an inflammatory cytokine storm and lethality, superantigens must bind directly to CD28. Blocking access of the superantigen to its CD28 receptor with peptides mimicking the contact domains in either toxin or CD28 suffices to protect mice effectively from lethal shock. Our finding that CD28 is a direct receptor of superantigen toxins broadens the scope of microbial pathogen recognition mechanisms.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. kaempfer@hebrew.edu.
authors.forename: Raymond
authors.initials: R
authors.lastname: Kaempfer
authors.forename: Gila
authors.initials: G
authors.lastname: Arad
authors.forename: Revital
authors.initials: R
authors.lastname: Levy
authors.forename: Dalia
authors.initials: D
authors.lastname: Hillman
authors.forename: Iris
authors.initials: I
authors.lastname: Nasie
authors.forename: Ziv
authors.initials: Z
authors.lastname: Rotfogel
mesh_terms: D000818:Animals; D001665:Binding Sites; D018106:CD28 Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D013297:Streptococcus pyogenes / Q000276:immunology; D018089:Superantigens / Q000737:chemistry / Q000276:immunology*; D014118:Toxins, Biological / Q000737:chemistry / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D018089:Superantigens; D014118:Toxins, Biological
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