Antagonist peptide for the treatment of bacterial superantigen toxic shock in a clinical or biowarfare setting

Abstract

A short peptide sequence derived from the dimer interface of CD28, an immune system co-stimulatory molecule, is claimed as an antagonist useful in the treatment of toxic shock triggered by bacterial pyrogenic exotoxins, often termed superantigens. These superantigens are a large family of functionally-related molecules produced by bacteria, such as Staphylococcus aureus and Streptococcus pyogenes. They are thought to act by massive activation of T lymphocytes to overproduce inflammatory cytokines. Examples of toxic shock could arise through food poisoning, bacterial sepsis or through weaponisation of the superantigens for biowarfare. The claimed compounds are shown to inhibit parameters of superantigen activation in several in vitro assays of T lymphocyte stimulation by superantigen or anti-CD28, and in a mouse model of toxic shock.

Keywords::

• antagonist peptide
• biowarfare
• superantigen
• T lymphocyte
• toxic shock