Kim J, Urban R G, Strominger J L, Wiley D C
Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115.
Science. 1994 Dec 16;266(5192):1870-4. doi: 10.1126/science.7997880.
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.
通过X射线晶体学确定了金黄色葡萄球菌超抗原中毒性休克综合征毒素-1（TSST-1）与人II类主要组织相容性分子（DR1）复合物的三维结构。DR1上TSST-1的结合位点与超抗原金黄色葡萄球菌肠毒素B（SEB）的结合位点重叠，但两种结合模式不同。SEB主要结合在DR1肽结合位点的一侧边缘，而TSST-1延伸至几乎一半的结合位点，并与组织相容性抗原的侧翼α螺旋和结合的肽接触。这种差异表明，T细胞受体（TCR）与TSST-1:DR1的结合方式与与DR1:肽或SEB:DR1的结合方式非常不同。这也表明TSST-1的结合可能依赖于肽，尽管程度低于TCR结合，这为TSST-1无法竞争性阻断SEB与细胞上所有DR1分子的结合（尽管TSST-1和SEB在DR1上的结合位点几乎完全重叠）提供了一种可能的解释，并提示超抗原激活T细胞可能受肽抗原指导的可能性。
