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CD28: Direct and Critical Receptor for Superantigen Toxins
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
* Author to whom correspondence should be addressed.
Received: 5 August 2013; in revised form: 30 August 2013 / Accepted: 5 September 2013 / Published: 9 September 2013
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.
Keywords: superantigen toxins; inflammatory cytokine storm; lethal toxic shock; biodefense; CD28 receptor; CD28 dimer interface
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Kaempfer, R.; Arad, G.; Levy, R.; Hillman, D.; Nasie, I.; Rotfogel, Z. CD28: Direct and Critical Receptor for Superantigen Toxins. Toxins 2013, 5, 1531-1542.
Kaempfer R, Arad G, Levy R, Hillman D, Nasie I, Rotfogel Z. CD28: Direct and Critical Receptor for Superantigen Toxins. Toxins. 2013; 5(9):1531-1542.
Kaempfer, Raymond; Arad, Gila; Levy, Revital; Hillman, Dalia; Nasie, Iris; Rotfogel, Ziv. 2013. "CD28: Direct and Critical Receptor for Superantigen Toxins." Toxins 5, no. 9: 1531-1542.