Defense against biologic warfare with superantigen toxins

Raymond Kaempfer*, Gila Arad, Revital Levy, Dalia Hillman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock. Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins. Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined. Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/α-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation. Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.

Original languageEnglish
Pages (from-to)520-523
Number of pages4
JournalIsrael Medical Association Journal
Volume4
Issue number7
StatePublished - 2002

Keywords

  • Antagonist peptide
  • Incapacitation
  • Superantigen
  • T cell activation
  • Toxic shock

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