Lamphear J G, Bohach G A, Rich R R
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
J Immunol. 1998 Mar 1;160(5):2107-14.
We have recently characterized an MHC class II-deficient human cell line, SW480, that supports the proliferation of purified human T cells in the presence of the staphylococcal enterotoxin and superantigen SEC1, but not the closely related isotypes SEC2 or SEC3. We now investigate the structural basis of this dichotomy and explore possible mechanisms that may account for it. Differences in activity between SEC1 and SEC2 were not attributable to differences in biochemical modification, to differences in Vbeta specificity, or to the potential to induce anergy. SEC2 inhibited SEC1-mediated T cell activation in the presence of SW480 cells, suggesting that SEC2 could compete with SEC1 for binding to the TCR but was unable to productively signal through the TCR. Utilizing a panel of hybrid enterotoxins we identified specific amino acids near the NH2-terminus of SEC1 that abrogated MHC class II-independent T cell activation, yet did not alter potency in the presence of class II+ APC. These residues mapped to the putative TCR binding domain of SEC1, and suggest that subtle differences in TCR binding affinity or the topology of the SEC1-TCR interaction can compensate for the lack of MHC class II and hence promote T cell proliferation.
我们最近鉴定了一种MHC II类缺陷型人细胞系SW480，该细胞系在葡萄球菌肠毒素和超抗原SEC1存在的情况下支持纯化的人T细胞增殖，但不支持密切相关的同型物SEC2或SEC3。我们现在研究这种二分法的结构基础，并探索可能解释它的机制。SEC1和SEC2之间的活性差异不归因于生化修饰的差异、Vβ特异性的差异或诱导无反应性的可能性。在SW480细胞存在的情况下，SEC2抑制SEC1介导的T细胞活化，这表明SEC2可以与SEC1竞争结合TCR，但无法通过TCR有效发出信号。利用一组杂交肠毒素，我们在SEC1的NH2末端附近鉴定了特定的氨基酸，这些氨基酸消除了不依赖MHC II类的T细胞活化，但在II类+抗原呈递细胞存在的情况下不改变效力。这些残基定位于SEC1的假定TCR结合域，并表明TCR结合亲和力或SEC1-TCR相互作用拓扑结构的细微差异可以弥补MHC II类的缺乏，从而促进T细胞增殖。
