A Review on CD28: Direct and Critical Receptor for Superantigen Toxins

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A Review on CD28: Direct and Critical Receptor for Superantigen Toxins

September 17, 2020 Chemical Science 0

Every adaptive immune response requires costimulation through the B7/CD28 axis, with CD28 on Tcells 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. Superantigens are among the most stable proteins known: They resist heat and
survive boiling, protease digestion, as well as acid denaturation. 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.

Author (s) Details

Raymond Kaempfer
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 9112102, Israel.

Gila Arad
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Revital Levy
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Dalia Hillman
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Iris Nasie
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Ziv Rotfogel
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

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