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Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock
Author(s) -
Arad Gila,
Hillman Dalia,
Levy Revital,
Kaempfer Raymond
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.6.921
Subject(s) - superantigen , biology , toxic shock syndrome , cytokine , immunology , microbiology and biotechnology , t cell , staphylococcus aureus , immune system , genetics , bacteria
Bacterial superantigens trigger an excessive, Th1‐cytokine response leading to toxic shock. We designed a peptide antagonist that inhibits SEB‐induced expression of human genes for IL‐2, IFN‐γ, and TNF‐β, cytokines that mediate shock. The peptide antagonist shows homology to a β‐strand‐hinge‐α‐helix domain that is conserved structurally in superantigens produced by Staphylococcus aureus and Streptococcus pyogenes yet remote from known binding sites for the major histocompatibility class II molecule and T‐cell receptor. For Th1‐cell activation, superantigens depend on this domain. The peptide protected mice against lethal challenge with SEB or SEA. Moreover, it rescued mice undergoing toxic shock. Surviving mice rapidly developed broad‐spectrum, protective immunity, which rendered them resistant to further lethal challenges with different staphylococcal and streptococcal superantigens. Thus, the lethal effect of superantigens, mediated by Th1 cytokines, can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells takes place.