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Science 16 December 1994: Vol. 266. no. 5192, pp. 1870 - 1874 DOI: 10.1126/science.7997880
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Articles
Science, Vol 266, Issue 5192, 1870-1874
Copyright © 1994 by American Association for the Advancement of Science
Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1
J Kim,
RG Urban,
JL Strominger,
and
DC Wiley
Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115.
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.
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