Functional characterization of streptococcal pyrogenic exotoxin J, a novel superantigen
Functional characterization of streptococcal pyrogenic exotoxin J, a novel superantigen
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DOI：
10.1128/iai.69.3.1381-1388.2001
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发表时间：
2001-03-01
影响因子：
3.1
通讯作者：
Schlievert, PM
中科院分区：
文献类型：
--
作者：
McCormick, JK;Pragman, AA;Schlievert, PM
链球菌中毒性休克综合征（STSS）是一种高度致命的急性发作性疾病，是侵袭性链球菌疾病的一个子集。大多数临床STSS病例与热原毒素超抗原（PTSAg）链球菌热原外毒素A或C（SPE A或C）相关，尽管已报告病例与这些外毒素中的任一种无关。最近的基因组测序项目已经揭示了许多开放阅读框架，其可能编码与SPEs A和C以及其他PTSAg相似的蛋白质。在此，我们描述了一种新的外毒素，称为链球菌致热外毒素J（SPE J），从大肠杆菌表达的纯化重组SPE i（rSPE J）刺激兔脾细胞和人外周血淋巴细胞的扩增，优先扩增展示V β 2，-3，-12，-14的人T细胞，和-17对它们的T细胞受体的作用，并且在低至5 × 10 - 6 μ g/ml的浓度下具有活性。此外，rSPE J诱导家兔发热，并在两种STSS模型中致死。在生物化学上，SPE J的预测分子量为24，444，等电点为7.7，并且缺乏形成许多PTSAg特有的胱氨酸环结构的能力，SPE J与SPE A、C、G和H、链球菌超抗原和链球菌促有丝分裂外毒素Z-2具有19.6、47.1、38.8、18.1、19.6和24.4%的同一性，与SPE C呈免疫交叉反应。第七个功能性链球菌PTSAg的表征提出了有关链球菌超抗原进化的重要问题。
Streptococcal toxic shock syndrome (STSS) is a highly lethal, acute-onset illness that is a subset of invasive streptococcal disease. The majority of clinical STSS cases have been associated with the pyrogenic toxin superantigens (PTSAgs) streptococcal pyrogenic exotoxin A or C (SPE A or C), although cases have been reported that are not associated with either of these exotoxins. Recent genome sequencing projects have revealed a number of open reading frames that potentially encode proteins with similarity to SPEs A and C and to other PTSAgs. Here, we describe the cloning, expression, purification, and functional characterization of a novel exotoxin termed streptococcal pyrogenic exotoxin J (SPE J), Purified recombinant SPE i (rSPE J) expressed from Escherichia coli stimulated the expansion of both rabbit splenocytes and human peripheral blood lymphocytes, preferentially expanded human T cells displaying V beta2, -3, -12, -14, and -17 on their T-cell receptors, and was active at concentrations as low as 5 x 10(-6) mug/ml. Furthermore, rSPE J induced fevers in rabbits and was lethal in two models of STSS. Biochemically, SPE J had a predicted molecular weight of 24,444 and an isoelectric point of 7.7 and lacked the ability to form the cystine loop structure characteristic of many PTSAgs, SPE J shared 19.6, 47.1, 38.8, 18.1, 19.6, and 24.4% identity with SPEs A, C, G, and H, streptococcal superantigen, and streptococcal mitogenic exotoxin Z-2, respectively, and was immunologically cross-reactive with SPE C. The characterization of a seventh functional streptococcal PTSAg raises important questions relating to the evolution of the streptococcal superantigens.