Regulation of antigen presentation machinery in human dendritic cells by recombinant adenovirus.
Regulation of antigen presentation machinery in human dendritic cells by recombinant adenovirus.
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重组腺病毒调节人树突状细胞中的抗原呈递机制。
DOI：
10.1007/s00262-008-0533-2
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Butterfield,LisaH
中科院分区：
文献类型：
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作者：
Vujanovic,Lazar;Whiteside,TheresaL;Potter,DouglasM;Chu,Jessica;Ferrone,Soldano;Butterfield,LisaH
重组腺病毒载体 (AdV) 是树突状细胞 (DC) 抗原工程的有效载体。用 AdV 改造表达全长肿瘤抗原的 DC 能够刺激抗原特异性多克隆 CD8+ 和 CD4+ T 细胞。为了确定 AdV 对 HLA I 类抗原呈递途径的影响，我们研究了 AdV 转导对人 DC 中抗原加工机器 (APM) 组件的影响。研究了 AdV 转导、成熟、APM 调节和 T 细胞激活之间的相互作用。 AdV 转导的 DC 的表型和细胞因子谱处于中间状态，介于未成熟 (iDC) 和成熟 DC (mDC) 之间。由于 AdV 转导，肽转运蛋白 TAP-1 和 TAP-2、HLA I 类肽负载分子伴侣 ERp57 以及共刺激表面分子 CD86 的表达在统计学上显着增加。 AdV 转导增强了 mDC 上 APM 成分和表面标记的表达，并且这些变化进一步受到 DC 成熟时间的调节。表达肿瘤相关抗原的成熟 DC 的工程刺激了更广泛的 CD8+ T 细胞库，能够识别免疫显性和次显性表位。这些数据确定了 AdV 转导 DC (AdV/DC) 中可能影响 T 细胞启动的分子变化，在癌症疫苗的设计中应予以考虑。
Recombinant adenoviral vectors (AdV) are potent vehicles for antigen engineering of dendritic cells (DC). DC engineered with AdV to express full length tumor antigens are capable stimulators of antigen-specific polyclonal CD8+ and CD4+ T cells. To determine the impact of AdV on the HLA class I antigen presentation pathway, we investigated the effects of AdV transduction on antigen processing machinery (APM) components in human DC. Interactions among AdV transduction, maturation, APM regulation and T cell activation were investigated. The phenotype and cytokine profile of DC transduced with AdV was intermediate, between immature (iDC) and matured DC (mDC). Statistically significant increases in expression were observed for peptide transporters TAP-1 and TAP-2, and HLA class I peptide-loading chaperone ERp57, as well as co-stimulatory surface molecule CD86 due to AdV transduction. AdV transduction enhanced the expression of APM components and surface markers on mDC, and these changes were further modulated by the timing of DC maturation. Engineering of matured DC to express a tumor-associated antigen stimulated a broader repertoire of CD8+ T cells, capable of recognizing immunodominant and subdominant epitopes. These data identify molecular changes in AdV-transduced DC (AdV/DC) that could influence T cell priming and should be considered in design of cancer vaccines.