Ubiquitin-fusion degradation pathway: a new strategy for inducing CD8 cells specific for mycobacterial HSP65.
Ubiquitin-fusion degradation pathway: a new strategy for inducing CD8 cells specific for mycobacterial HSP65.
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DOI：
10.1016/j.bbrc.2007.11.009
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发表时间：
2008-01
影响因子：
3.1
通讯作者：
Jianying Shen;H. Hisaeda;B. Chou;Qingsheng Yu;Liping Tu;K. Himeno
中科院分区：
文献类型：
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作者：
Jianying Shen;H. Hisaeda;B. Chou;Qingsheng Yu;Liping Tu;K. Himeno
泛素-蛋白酶体系统（UPS）在诱导MHC i类限制性CD8+T细胞中起着不可或缺的作用。在这项研究中，我们利用UPS诱导CD8+T细胞特异性针对HSP65分枝杆菌（mHSP65），这是抗结核分枝杆菌感染的主要候选疫苗之一。构建了编码鼠泛素与mHSP65融合蛋白的pU-HSP65嵌合DNA，用基因枪轰击的方法免疫C57BL/6 （B6）小鼠。与仅编码mHSP65的DNA免疫的小鼠相比，用嵌合DNA免疫的小鼠对转染mHSP65基因（HSP65/B16F1）的同基因B16F1黑色素瘤细胞的攻击具有强大的抵抗力。与后一组小鼠相比，前一组小鼠的脾细胞对HSP65/B16F1细胞表现出更高的细胞毒活性，并且含有更多的颗粒酶B或IFN-γ-产生CD8+T细胞。
The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8+T cells. In this study, we exploited UPS to induce CD8+T cells specific for mycobacterial HSP65 (mHSP65), one of the leading vaccine candidates against infection with Mycobacterium tuberculosis. A chimeric DNA termed pU-HSP65 encoding a fusion protein between murine ubiquitin and mHSP65 was constructed, and C57BL/6 (B6) mice were immunized with the DNA using gene gun bombardment. Mice immunized with the chimeric DNA acquired potent resistance against challenge with the syngeneic B16F1 melanoma cells transfected with the mHSP65 gene (HSP65/B16F1), compared with those immunized with DNA encoding only mHSP65. Splenocytes from the former group of mice showed a higher grade of cytotoxic activity against HSP65/B16F1 cells and contained a larger number of granzyme B- or IFN-γ-producing CD8+T cells compared with those from the latter group of mice.