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CpG免疫调节序列最新研究进展

Recent advances in CPG immunoregulatory sequence

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【作者】 施海晶; 胡云章;

【Author】 SHI Hai-Jing, HU Yun-Zhang (Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union of Medical College, Kunming 650107, China)

【机构】 中国医学科学院!中国协和医科大学医学生物研究所; 昆明650107;

【摘要】 细菌等非脊椎动物的 DNA和人工合成的寡聚核苷酸(ODN)中所包含的免疫刺激 CPG序列(CpG-S)被抗原呈递细胞(APC)摄入后;经由pH依赖的胞内体酸化,产生活性氧(ROS);然后分别活化转录因子 AP-1和 NF-kB,激活细胞因子等基因的表达,从而刺激机体产生免疫应答,包括刺激多种免疫活性细胞分泌细胞因子,使机体产生快速高水平的抗体应答及细胞免疫应答。能产生这种刺激作用的最适序列为 CpG 5’端为两嘌呤, 3’端为两嘧啶,并且具有种属特异性。 CpG DNA的佐剂特性将在未来疫苗研究开发中起到重要作用。此外,在基因治疗设计中加入最新发现的免疫抑制CpG序列(CpG-N)则可抑制针对目的蛋白的免疫应答,从而加强目的基因的治疗效果。

【Abstract】 Bacterial DAN and synthetic oligodeoxynucleotides(ODN) containing unmethylated CpG motif which termed immunostimulatory DNA sequence(CpG-S)can be taken up by antigen presenting cells into mature endosome where it is acdified and degraded, this step is coupled to the rapid generation of intracellular reactive oxygen species(ROS), then activate transcription factor NF--GB and AP--l, which induces the expression of cytokines. That is to say, CpG DNA can trigger innate immune defenses including the activation of various immune cell subsets, and also induce production of a numbers of cytokines and antibodys. The optimal CPG motif is CPG flanked by two 5’ purines and 3’ pyrimidines, and it is species specific. It is important that CpG-S acts as effective immune adjuvants in the future vaccine research and development. On the other hand, the field of gene therapy may be benefit from the discovery of neutralizing motif(CpG-N)because they can prevent or reduce the induction of host immune responses, and increase the efficiency of gene therapy.

【关键词】 CpG; DNA; 免疫调节; 佐剂; 基因治疗;
【Key words】 CpG DNA; immunoregulator; adjuvant; gene therapy;
  • 【文献出处】 生命科学 ,CHINESE BULLETIN OF LIFE SCIENCES , 编辑部邮箱 ,2000年05期
  • 【分类号】Q459.9
  • 【被引频次】11
  • 【下载频次】202
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