Recombinant expression and neutralizing activity of an MHC class II binding epitope of toxic shock syndrome toxin-1.
Toxic shock syndrome (TSS) is caused by the staphylococcal superantigen, TSST-1. The MHC class II binding domain of TSST-1 containing a conserved sequence with other related staphylococcal enterotoxins, comprising TSST-1 residues 47-64 [(T(47-64)], was expressed as a fusion protein with either glutathione-S-transferase (GST(47-64)), filamentous phage coat protein (pIII(47-64)), or E. coli outer membrane porin protein (OprF(47-64)), or synthesized as a peptide conjugated to bovine serum albumin, BSA(47-64). GST(47-64), OprF(47-64) and BSA(47-64), but not pIII(47-64), all induced high-titer T(47-64)-specific antibodies in Balb/c mice. However, only anti-GST(47-64) antibodies inhibited (125)I-TSST-1 binding to MHC class II and abrogated TSST-1-induced T cell mitogenesis and TNFalpha secretion in human peripheral blood mononuclear cells. Purified GST(47-64) also inhibited (125)I-TSST-1 binding in a dose-dependent manner. These findings suggest that GST(47-64) may have potential as a recombinant peptide vaccine or TSST-1 receptor inhibitor against TSS.
Rubinchik
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Division of Infectious Diseases, Department of Medicine, University of British Columbia, Canadian Bacterial Disease Network, and Vancouver Hospital Health Sciences Center, Vancouver, Canada.
Chow
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AW
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins; D001665:Binding Sites; D004768:Enterotoxins / Q000276:immunology*; D000939:Epitopes; D005982:Glutathione Transferase / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology*
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D007106:Immune Sera; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; C030107:enterotoxin F, Staphylococcal; D005982:Glutathione Transferase