Exogenous antigens are processed through the endoplasmic reticulum-associated degradation (ERAD) in cross-presentation by dendritic cells
Exogenous antigens are processed through the endoplasmic reticulum-associated degradation (ERAD) in cross-presentation by dendritic cells
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DOI：
10.1093/intimm/dxh184
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Yahara, I
中科院分区：
文献类型：
--
作者：
Imai, J;Hasegawa, H;Yahara, I
抗原交叉递呈在感染和肿瘤免疫中是至关重要的，在这些免疫中，细胞毒性T淋巴细胞是由树突状细胞特异性地配备细胞器来呈递具有主要组织相容性复合体(MHC)I类分子的外源抗原。为了研究抗原交叉提呈的分子机制，我们使用了一个小鼠树突状细胞系DC2.4作为模型系统，该细胞系能够递送具有MHC I类的可溶性抗原，例如卵蛋白(OVA)。在这里，我们证明了外源添加的OVA积累在内质网(ER)和晚期内体中，然后通过Sec61转运体复合体逆行转运到细胞质中，并且CHIP作为E3泛素连接酶作用于蛋白酶体降解OVA。这种机制在本质上与内质网相关降解(ERAD)在分泌物和膜蛋白的质量控制中是相同的。
Antigen cross-presentation is critical in infectious and tumor immunity where cytotoxic T lymphocytes are induced by dendritic cells specifically equipped with cellular machineries to present exogenous antigens with major histocompatibility complex (MHC) class I molecules. To examine molecular mechanisms of antigen cross-presentation, we employed as a model system a murine dendritic cell line DC2.4 capable of presenting soluble antigens such as ovalbumin (OVA) with MHC class I. Here, we demonstrate that exogenously added OVA is accumulated in the endoplasmic reticulum (ER) and late endosomes followed by retrograde transport to the cytoplasm through the Sec61 transporter complexes, and that CHIP functions as an E3 ubiquitin-ligase for OVA degradation by proteasomes. This mechanism is essentially the same as that known as the ER-associated degradation (ERAD) in the quality control of secretary and membrane proteins.