title: Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1.
abstract: The three-dimensional structure of a Staphylococcus aureus superantigen, toxic shock syndrome toxin-1 (TSST-1), complexed with a human class II major histocompatibility molecule (DR1), was determined by x-ray crystallography. The TSST-1 binding site on DR1 overlaps that of the superantigen S. aureus enterotoxin B (SEB), but the two binding modes differ. Whereas SEB binds primarily off one edge of the peptide binding site of DR1, TSST-1 extends over almost one-half of the binding site and contacts both the flanking alpha helices of the histocompatibility antigen and the bound peptide. This difference suggests that the T cell receptor (TCR) would bind to TSST-1:DR1 very differently than to DR1:peptide or SEB:DR1. It also suggests that TSST-1 binding may be dependent on the peptide, though less so than TCR binding, providing a possible explanation for the inability of TSST-1 to competitively block SEB binding to all DR1 molecules on cells (even though the binding sites of TSST-1 and SEB on DR1 overlap almost completely) and suggesting the possibility that T cell activation by superantigen could be directed by peptide antigen.
authors.affiliation: Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: R G
authors.initials: RG
authors.lastname: Urban
authors.forename: J L
authors.initials: JL
authors.lastname: Strominger
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D001427:Bacterial Toxins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013211:Staphylococcus aureus; D018089:Superantigens / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D015798:HLA-DR1 Antigen; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal