Humanlike immune response of human leukocyte antigen-DR3 transgenic mice to staphylococcal enterotoxins: a novel model for superantigen vaccines.

Abstract

This study examined the biologic responses of transgenic mice expressing human leukocyte antigen (HLA)-DR3 and human CD4 molecules, in the absence of murine major histocompatibility complex (MHC) class II molecules (Ab(0)), to staphylococcal enterotoxins (SEs) and evaluated protective immunity of a nonsuperantigen form of SEB against wild-type holotoxin. HLA-DR3 transgenic mice responded to several log lower concentrations of SEs and secreted higher levels of proinflammatory cytokines than did wild-type mice. Vaccination of transgenic mice with a nonsuperantigenic form of SEB induced high levels of neutralizing anti-SEB antibodies, which protected the mice from a surge in proinflammatory cytokine secretion after SEB challenge. The humanlike responses of the transgenic mice to SEs support the hypothesis that these mice represent an appropriate model to examine vaccines and therapeutics against SEs. This is thought to be the first report of examination of a vaccine against SEB in the context of human MHC class II receptors.