title: 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.
authors.affiliation: Dept. of Cell Biology and Biochemistry, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011, USA. luis.dasilva@amedd.army.mil
authors.forename: Luis
authors.initials: L
authors.lastname: DaSilva
authors.forename: Brent C
authors.initials: BC
authors.lastname: Welcher
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
authors.forename: Chella S
authors.initials: CS
authors.lastname: David
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D015803:HLA-DR3 Antigen / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D015704:CD4 Antigens; D004768:Enterotoxins; D015803:HLA-DR3 Antigen; D018089:Superantigens