Broad-Spectrum in-vivo effective superantigen toxin antagonists based on the interaction between CD28 and the superantigen and uses thereof

摘要

The present invention relates to a superantigen binding site within the CD28 molecule, comprising part or all of the amino acid sequence H V K G K H L C P (also denoted by SEQ ID NO: 3). This site specifically and directly binds to a superantigen through a spatially conserved domain of a pyrogenic exotoxin, which domain is not involved in the binding of any one of MHC Class II molecules and TCR. The direct binding between the CD28 molecule and the superantigen at this site facilitates the binding of a B7-2 ligand to CD28, and is essential for activation of Th1 lymphocytes as defined by the induction of IL-2 and/or IFN-g gene expression. The present invention provides substances which inhibit this interaction and therefore inhibit the superantigen mediated activation of Th1 lymphocytes, and thus protect against toxic shock and may also elicit protective immunity.The present invention further relates to use of the CD28 molecule or any fragment thereof comprising the s-Ag binding site in a method of screening for a test substance which specifically binds to the CD28 molecule and is capable of antagonizing pyrogenic exotoxin-mediated activation of Th1 lymphocytes.