The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells
The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells
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DOI：
10.1093/intimm/dxl005
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发表时间：
2006-05-01
影响因子：
4.4
通讯作者：
Himeno, K
中科院分区：
文献类型：
--
作者：
Duan, XF;Hisaeda, H;Himeno, K
MUT 1是一种H-2K（B）限制性8聚体CTL表位，在来源于C57 BL/6（B6）小鼠的刘易斯肺癌（3LL）肿瘤细胞中表达。我们构建了编码泛素融合MUT 1的嵌合基因（pUB-MUT 1）。通过使用基因枪，在用3LL肿瘤细胞攻击之前用该基因免疫B6小鼠。在用pUB-MUT 1免疫的小鼠中，肿瘤生长和肺转移被显著抑制，但仅在用MUT 1基因（pMUT）单独免疫的小鼠中轻微抑制。通过体外实验和用相应抗体体内去除细胞，证实CD 8（+）T细胞是最终效应细胞。在蛋白酶体免疫亚单位LMP 7缺陷的小鼠中，抗肿瘤免疫受到严重抑制。此外，缺乏蛋白酶体调节剂PA 28 α/β的小鼠未能获得保护性免疫。因此，泛素融合降解途径的应用甚至在用编码单个CTL表位的基因免疫以诱导特异性和活性CD 8（+）T细胞中也是有用的。
MUT1 is an H-2K(b)-restricted 8-mer CTL epitope expressed in Lewis lung carcinoma (3LL) tumor cells derived from C57BL/6 (B6) mice. We constructed a chimeric gene encoding ubiquitin-fused MUT1 (pUB-MUT1). By using a gene gun, B6 mice were immunized with the gene prior to challenge with 3LL tumor cells. Tumor growth and lung metastasis were prominently suppressed in mice immunized with pUB-MUT1 but only slightly in those immunized with the MUT1 gene (pMUT) alone. CD8(+) T cells were confirmed to be the final effector by in vitro experiments and in vivo removal of the cells with a corresponding antibody. Anti-tumor immunity was profoundly suppressed in mice deficient in an immuno-subunit of proteasome, LMP7. Furthermore, mice deficient in a proteasome regulator, PA28 alpha/beta, failed to acquire protective immunity. Thus, application of the ubiquitin-fusion degradation pathway was useful even in immunization with genes encoding a single CTL epitope for induction of specific and active CD8(+) T cells.