Zhang Guojun, Xu Mingkai, Sun Jian, Li Hongyi, Yang Hongli, Zhang Huiwen, Zhang Chenggang
Institute of Applied Ecology, University of Chinese Academy of Sciences, Shenyang 110016, Liaoning, China.
Sheng Wu Gong Cheng Xue Bao. 2013 Jun;29(6):803-13.
As a superantigen protein, 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 102-106 of native SEC2 were substituted for WWH, WWT and WWP by over-lap PCR, and three mutants named ST-1, ST-2 and ST-3 were obtained. Stimulating activity to murine lymphocytes proliferation and inhibiting activity to tumor cell growth of the three mutants were significantly improved compared with the native SEC2. Febrile activities of ST-1 and ST-3 were comparable with the native SEC2, but ST-2 showed markedly increased febrile activity than native SEC2. Moreover, the levels of IL-2, IFN-gamma and TNF-alpha secreted by T cells stimulated with the three mutants were significantly improved, which might be the possible reason for enhanced tumor cell growth inhibition activities. Furthermore, mVbeta8.2 gene transcription levels of murine splenocytes stimulated by the three mutants were dramatically increased compared with native SEC2, suggesting their increased affinities to TCR mVbeta8.2 molecular, which might be the main reason for their enhanced superantigen activities.
作为一种超抗原蛋白,葡萄球菌肠毒素C2(SEC2)即使在极低浓度下也能有效激活免疫系统,这一特性可应用于肿瘤和传染病的辅助治疗。为了增强SEC2的超抗原活性,通过重叠PCR将天然SEC2第102-106位的残基替换为WWH、WWT和WWP,获得了三个突变体,分别命名为ST-1、ST-2和ST-3。与天然SEC2相比,这三个突变体对小鼠淋巴细胞增殖的刺激活性和对肿瘤细胞生长的抑制活性均显著提高。ST-1和ST-3的发热活性与天然SEC2相当,但ST-2的发热活性比天然SEC2明显增强。此外,用这三个突变体刺激T细胞分泌的IL-2、IFN-γ和TNF-α水平显著提高,这可能是肿瘤细胞生长抑制活性增强的原因。此外,与天然SEC2相比,这三个突变体刺激小鼠脾细胞的mVbeta8.2基因转录水平显著增加,表明它们与TCR mVbeta8.2分子的亲和力增加,这可能是它们超抗原活性增强的主要原因。