Antigen-specific CD8+ T cells induced by the ubiquitin fusion degradation pathway
Antigen-specific CD8+ T cells induced by the ubiquitin fusion degradation pathway
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DOI：
10.1016/j.bbrc.2007.11.034
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发表时间：
2008-01-25
影响因子：
3.1
通讯作者：
Himeno, Kunisuke
中科院分区：
文献类型：
--
作者：
Imai, Takashi;Duan, Xuefeng;Himeno, Kunisuke
我们已经开发了一种编码泛素（Ub）和N端靶蛋白融合蛋白的DNA疫苗，用于有效诱导抗原特异性CD 8（+）T细胞。一系列编码与突变的Ub融合的模型抗原卵清蛋白（OVA）的表达质粒。构建了Western blotting分析表明，Ub与OVA之间存在3种不同的结合位点。具有C-末端甘氨酸的天然Ub容易从OVA解离;另一方面，人工突变的Ub，其C-末端氨基酸已被交换为缬氨酸或精氨酸，与多肽稳定地结合，而具有C-末端丙氨酸的Ub部分解离。DNA疫苗诱导OVA特异性CD 8（+）T细胞的能力与Ub与OVA融合的稳定性密切相关。我们的策略可用于优化基因疫苗诱导CD 8（+）T细胞的效果。(c)2007爱思唯尔公司All rights reserved.
We have developed a DNA vaccine encoding a fusion protein of ubiquitin (Ub) and target proteins at the N-terminus for effective induction of antigen-specific CD8(+) T cells. A series of expression plasmids encoding a model antigen, ovalbumin (OVA), fused with mutated Ub. was constructed. Western blotting analyses using COS7 cells transfected with these plasmids revealed that there were three types of amino acid causing different bindin capacities between Ub and OVA. Natural Ub with a C-terminal glycine readily dissociated from OVA; on the other hand, artificially mutated Ub, the C-terminal amino acid of which had been exchanged to valine or arginine, stably united with the polypeptide, while Ub with a C-terminal alanine partially dissociated. The ability of DNA vaccination to induce OVA-specific CD8(+) T cells closely correlated with the stability of Ub fusion to OVA. Our strategy could be used to optimize the effect of genetic vaccines on the induction of CD8(+) T cells. (c) 2007 Elsevier Inc. All rights reserved.