Tiedemann R E, Fraser J D
Department of Molecular Medicine, University of Auckland School of Medicine, New Zealand.
J Immunol. 1996 Nov 1;157(9):3958-66.
Two binding sites for MHC class II have previously been identified on opposite sides of the superantigen, staphylococcal enterotoxin A (SEA). The sites mediate separate binding reactions with nonoverlapping regions of class II, and in solution cause SEA to complex with purified HLA-DR1 to form DR1.SEA2 trimers. Here, a set of complementary SEA class II-binding mutants was used to study the interaction of SEA with cell surface MHC class II. The results indicate that both class II binding sites are required on the same toxin molecule for maximal activity, demonstrating that simultaneous ligation of two MHC class II molecules on APCs by a single SEA is essential for effective superantigen function. Coalescence of MHC class II by SEA results in protein tyrosine kinase activation and contributes to the induction of cell:cell adhesion, pro-inflammatory cytokine gene transcription, and T cell proliferation.
先前已在超抗原葡萄球菌肠毒素A（SEA）的两侧鉴定出两个MHC II类结合位点。这些位点介导与II类非重叠区域的单独结合反应，并在溶液中使SEA与纯化的HLA-DR1复合形成DR1.SEA2三聚体。在这里，一组互补的SEA II类结合突变体被用于研究SEA与细胞表面MHC II类的相互作用。结果表明，同一毒素分子上的两个II类结合位点对于最大活性都是必需的，这表明单个SEA同时连接APC上的两个MHC II类分子对于有效的超抗原功能至关重要。SEA使MHC II类聚集导致蛋白酪氨酸激酶激活，并有助于诱导细胞间粘附、促炎细胞因子基因转录和T细胞增殖。
