Fleischer B, Gerardy-Schahn R, Metzroth B, Carrel S, Gerlach D, Köhler W
1. Department of Medicine, University of Mainz, FRG.
J Immunol. 1991 Jan 1;146(1):11-7.
The enterotoxins produced by Staphylococcus aureus are the most potent mitogens known. They belong to a group of distantly related mitogenic toxins that differ in other biologic activities. In this study we have compared the molecular mechanisms by which these mitogens activate human T lymphocytes. We used the staphylococcal enterotoxins A to E, the staphylococcal toxic shock syndrome toxin, the streptococcal erythrogenic toxins A and C (scarlet fever toxins, erythrogenic toxins (ET)A, ETC), and the soluble mitogen produced by Mycoplasma arthritidis. We found that all these toxins can activate both CD4+ and CD8+ T cells and require MHC class II expression on accessory and target cells. However, T cells could be activated in the absence of class II molecules if the toxins ETA or SEB were co-cross-linked on beads together with anti-CD8 or anti-CD2 antibodies. Enterotoxins, toxic shock syndrome toxin and scarlet toxins stimulate a major fraction of human T cells, and show preferential, but not exclusive, stimulation of T cells carrying certain TCR V beta. In contrast, the mitogen of M. arthritidis, a pathogen for rodents stimulates only a minority of human T cells but activates a major fraction of murine T cells. Analysis of human T cell clones expressing V beta 5 or V beta 8 TCR showed that these clones responded also to those toxins that did not stimulate V beta 5+ and V beta 8+ T cells in bulk cultures. These results indicate that different TCR bind to these toxins with different affinities and that the specificity of the TCR-V beta-toxin interaction is quantitative rather than qualitative in nature. Taken together our findings suggest that these toxins use a common mechanism of T cell activation. They are functionally bivalent proteins crosslinking MHC class II molecules with variable parts of the TCR. Besides V beta, other parts of the TCR must be involved in this binding. The finding that murine T cells responded more weakly to the toxins produced by the human-pathogenic bacteria than to the Mycoplasma mitogen could indicate that the toxins have been adapted to the host's immune system in evolution.
金黄色葡萄球菌产生的肠毒素是已知最有效的促细胞分裂剂。它们属于一组亲缘关系较远的促有丝分裂毒素，在其他生物学活性方面有所不同。在本研究中，我们比较了这些促细胞分裂剂激活人T淋巴细胞的分子机制。我们使用了葡萄球菌肠毒素A至E、葡萄球菌中毒性休克综合征毒素、链球菌致热外毒素A和C（猩红热毒素、致热外毒素（ET）A、ETC）以及关节炎支原体产生的可溶性促细胞分裂剂。我们发现所有这些毒素都能激活CD4+和CD8+ T细胞，并且需要辅助细胞和靶细胞上表达MHC II类分子。然而，如果毒素ETA或SEB与抗CD8或抗CD2抗体一起在珠子上共交联，则T细胞可以在没有II类分子的情况下被激活。肠毒素、中毒性休克综合征毒素和猩红热毒素刺激大部分人T细胞，并对携带某些TCR Vβ的T细胞表现出优先但非排他性的刺激。相比之下，关节炎支原体的促细胞分裂剂，一种啮齿动物病原体，仅刺激少数人T细胞，但激活大部分鼠T细胞。对表达Vβ5或Vβ8 TCR的人T细胞克隆的分析表明，这些克隆也对在大量培养中不刺激Vβ5+和Vβ8+ T细胞的那些毒素有反应。这些结果表明不同的TCR以不同的亲和力结合这些毒素，并且TCR-Vβ-毒素相互作用的特异性本质上是定量的而非定性的。综合我们的发现表明这些毒素使用共同的T细胞激活机制。它们是功能性二价蛋白，将MHC II类分子与TCR的可变部分交联。除了Vβ，TCR的其他部分也必须参与这种结合。鼠T细胞对人病原菌产生的毒素的反应比对支原体促细胞分裂剂的反应更弱这一发现可能表明这些毒素在进化过程中已适应宿主的免疫系统。
