Nagata T, Uchijima M, Yoshida A, Kawashima M, Koide Y
Department of Microbiology and Immunology, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu, 431-3192, Japan.
Biochem Biophys Res Commun. 1999 Aug 2;261(2):445-51. doi: 10.1006/bbrc.1999.1050.
Interspecific difference of codon usage is one of the major obstacles for effective induction of specific immune responses against bacteria and protozoa by DNA immunization. Using genes encoding major histocompatibility complex class I-restricted cytotoxic T-lymphocyte (CTL) epitopes, derived from an intracellular bacterium, Listeria monocytogenes and a mouse malaria parasite, Plasmodium yoelii, we report here that the codon optimization level of the genes is not precisely proportional to, but does correlate well with the translational efficiency in mammalian cells, which is concomitantly associated with the induction level of specific CTL response in the mouse. These results suggest that DNA immunization using the gene codon-optimized to mammals through the entire region is very effective.
密码子使用的种间差异是通过DNA免疫有效诱导针对细菌和原生动物的特异性免疫反应的主要障碍之一。我们使用编码主要组织相容性复合体I类限制性细胞毒性T淋巴细胞(CTL)表位的基因,这些基因来源于细胞内细菌单核细胞增生李斯特菌和小鼠疟原虫约氏疟原虫,在此报告基因的密码子优化水平并非与哺乳动物细胞中的翻译效率精确成正比,但确实与之密切相关,而这又与小鼠中特异性CTL反应的诱导水平相关。这些结果表明,使用在整个区域对哺乳动物进行密码子优化的基因进行DNA免疫非常有效。