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.
View Book :- https://bp.bookpi.org/index.php/bpi/catalog/book/253
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