The involvement of immunoproteasomes in induction of MHC class I-restricted immunity targeting Toxoplasma SAG1
The involvement of immunoproteasomes in induction of MHC class I-restricted immunity targeting Toxoplasma SAG1
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DOI：
10.1016/j.micinf.2005.10.023
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Himeno, Kunisuke
中科院分区：
文献类型：
--
作者：
Ishii, Kazunari;Hisaeda, Hajime;Himeno, Kunisuke
泛素-蛋白酶体系统（ubiquitin-proteasome system，UPS）在诱导MHC I类限制性CD 8（+）T细胞中起着不可或缺的作用，通过构建小鼠泛素与弓形虫抗原SAG 1融合蛋白的嵌合DNA，UPS被用于抗弓形虫细胞内DNA疫苗的开发。SAG 1肽在用嵌合DNA转染的抗原呈递细胞（APC）中迅速降解。然而，通过将APC与蛋白酶体抑制剂epoxomicin孵育来阻碍降解。用该DNA接种的小鼠获得了由MHC I类限制性CD 8（+）T细胞介导的针对高毒性弓形虫感染的有效保护性免疫。免疫的加速降解和诱导依赖于UPS，因为缺乏20 S蛋白酶体的免疫亚基LMP 7的小鼠失去了这些功能，尽管它们不依赖于蛋白酶体调节剂PA 28 α/β复合物。(c)2005年，Elsevier SAS。All rights reserved.
The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8(+) T cells and was exploited in the development of a DNA vaccine against the intracellular protozoan Toxoplasma gondii by constructing a chimeric DNA encoding a fusion protein between murine ubiquitin and the toxoplasma antigen SAG1. The SAG1 peptide was promptly degraded in antigen-presenting cells (APCs) transfected with the chimeric DNA. Degradation, however, was hampered by incubating the APCs with the proteasome inhibitor epoxomicin. Mice vaccinated with the DNA acquired potent protective immunity mediated by MHC class I-restricted CD8(+) T cells against infection by the highly virulent Toxoplasma. The accelerated degradation and induction of immunity were dependent on the UPS since mice lacking an immuno-subunit of 20S proteasome, LMP7, lost these functions, although they were independent of the proteasome regulator PA28 alpha/beta complex. (c) 2005 Elsevier SAS. All rights reserved.