【作者】 张国俊； 徐明恺； 姚崧源； 张惠文； 张成刚；

【Author】 Guojun Zhang;Mingkai Xu;Songyuan Yao;Huiwen Zhang;Chenggang Zhang;Institute of Applied Ecology,University of Chinese Academy of Sciences;University of the Chinese Academy of Sciences;

【机构】 中国科学院大学沈阳应用生态研究所； 中国科学院大学；

【摘要】 金黄色葡萄球菌肠毒素C2(Staphylococcal enterotoxin C2,SEC2)作为一种超级抗原蛋白,极微量即可有效激活机体免疫系统,这一特性可应用于对肿瘤和感染性疾病的辅助治疗。为了增强SEC2的超抗原活性,应用定点突变方法将SEC2中的20位T氨基酸残基突变为L,获得突变体ST-5。突变体刺激小鼠淋巴细胞增殖活性和肿瘤细胞生长抑制活性与野生型SEC2相比均有显著提高。此外,突变体体外刺激淋巴细胞分泌IL-2、IFN-γ和TNF-α的水平也显著提高,这可能是导致突变体具有较高肿瘤细胞生长抑制活性的原因。进一步实验发现,突变体刺激下,小鼠脾淋巴细胞m Vβ8.2和8.3基因的转录水平较野生型SEC2显著增加,暗示突变体对TCR m Vβ8.2和8.3分子亲和力的提高,可能是其超抗原活性增强的主要原因。更多还原

【Abstract】 As a superantigen, Staphylococcal enterotoxin C2(SEC2) activates the immune system effectively even in extremely low concentrations, and this property could be applied in adjuvant therapy against tumors and infectious diseases. In order to enhance the superantigen activity of SEC2, the residues at position 20 of native SEC2 were substituted for L by site-directed mutagenesis, and the mutant named ST-5 was obtained. Stimulating activity to murine lymphocytes proliferation and inhibiting activity to tumor cell growth of ST-5 were significantly improved compared with native SEC2. Moreover, the levels of IL-2, IFN-γ, and TNF-α secreted by T cells stimulated with ST-5 were significantly improved, which might be the possible reason for enhanced tumor cell growth inhibition activities. Furthermore, m Vβ8.2 and 8.3 gene transcription levels of murine splenocytes stimulated by ST-5 were dramatically increased compared with native SEC2, suggesting the increased affinities to TCR m Vβ8.2 and 8.3 molecular, which might be the reason for the enhanced superantigen activity of ST-5.更多还原