Monday S R, Vath G M, Ferens W A, Deobald C, Rago J V, Gahr P J, Monie D D, Iandolo J J, Chapes S K, Davis W C, Ohlendorf D H, Schlievert P M, Bohach G A
Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow 83844, USA.
J Immunol. 1999 Apr 15;162(8):4550-9.
Certain strains of Staphylococcus aureus express one or both of two related, but immunologically distinct, exfoliative toxins (ETA and ETB). These toxins induce the symptoms associated with staphylococcal scalded skin syndrome. Both ETs have been shown to stimulate T cell proliferation. Recently, it was reported that ETA is a superantigen that stimulates T cells bearing human Vbeta2 or several murine Vbetas. However, other investigators have proposed that the superantigenicity reported for ETA resulted from contaminants in commercial preparations. This present study addresses those conflicting reports by assessing the biological and immunologic activities of highly purified rETs. ETA and ETB required APCs to induce selective polyclonal expansion of several human Vbetas (huVbetas), although, neither toxin expanded huVbeta2. ETB induced expansion of murine T cells bearing Vbetas 7 and 8, those that have the highest homology to the huVbetas expanded by ETA and ETB. Although flow cytometry of ETB-stimulated T cells matched PCR results, stimulation by ETA reduced percentages of T cells positive for several huVbetas that had been shown to have increased levels of mRNA transcripts. ETA and ETB induced contrasting reactions in vivo. In rabbits, ETB was moderately pyrogenic and enhanced susceptibility to lethal shock, while ETA lacked both activities. Predictions based on comparisons with other superantigens suggest molecular regions potentially involved in receptor binding in the ETA crystal structure and a modeled ETB three-dimensional structure. These results show that ETs are superantigens with unique properties that could account for the discrepancies reported.
某些金黄色葡萄球菌菌株表达两种相关但免疫原性不同的剥脱毒素（ETA和ETB）中的一种或两种。这些毒素会引发与葡萄球菌烫伤样皮肤综合征相关的症状。两种毒素均已显示能刺激T细胞增殖。最近有报道称ETA是一种超抗原，可刺激携带人Vβ2或几种鼠类Vβ的T细胞。然而，其他研究人员提出，报道的ETA的超抗原性是由商业制剂中的污染物导致的。本研究通过评估高度纯化的重组剥脱毒素（rETs）的生物学和免疫活性来解决这些相互矛盾的报道。ETA和ETB需要抗原呈递细胞（APCs）来诱导几种人Vβ（huVβ）的选择性多克隆扩增，不过，两种毒素都不会使huVβ2扩增。ETB诱导携带Vβ7和Vβ8的鼠类T细胞扩增，这两种Vβ与被ETA和ETB扩增的huVβ具有最高的同源性。尽管对ETB刺激的T细胞进行流式细胞术检测的结果与聚合酶链反应（PCR）结果相符，但ETA刺激会降低几种已显示mRNA转录水平升高的huVβ阳性T细胞的百分比。ETA和ETB在体内引发了不同的反应。在兔子中，ETB有中度致热原性，并增强了对致死性休克的易感性，而ETA则缺乏这两种活性。基于与其他超抗原比较的预测表明，ETA晶体结构和模拟的ETB三维结构中可能存在与受体结合相关的分子区域。这些结果表明，剥脱毒素是具有独特性质的超抗原，这可能解释了所报道的差异。
