The expression and function of cathepsin E in dendritic cells
The expression and function of cathepsin E in dendritic cells
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DOI：
10.4049/jimmunol.174.4.1791
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发表时间：
2005-02-15
影响因子：
4.4
通讯作者：
Terrazzini, N
中科院分区：
文献类型：
--
作者：
Chain, BM;Free, P;Terrazzini, N
组织蛋白酶E是一种天冬氨酸蛋白酶，参与了11类MHC途径中的Ag加工。在这项研究中，我们记录了组织蛋白酶E消息和蛋白在人类髓系树突状细胞中的存在，人类髓系树突状细胞是免疫系统的主要抗原原细胞。组织蛋白酶E位于核周室，可能构成内质网的一部分，也存在于细胞膜正下方的周围室，其分布与德克萨斯红葡聚糖在内吞作用2分钟内的分布相似。为了研究组织蛋白酶E在加工过程中的作用，通过可切割的二硫键将微生物天冬氨酸蛋白酶抑制剂胃抑素与甘露糖化牛血清白蛋白连接起来，合成了一种新的可溶性靶向抑制剂。在无细胞检测和树突状细胞内，这种抑制物被证明能阻断组织蛋白酶D/E的活性。该抑制剂阻断了野生型和组织蛋白酶D缺陷小鼠的树突状细胞将完整的OVA呈递给同源T细胞的能力，但不能呈现OVA衍生的多肽。因此，这些数据支持组织蛋白酶E在树突状细胞内11类MHC抗原处理途径中具有重要的非冗余作用的假设。
Cathepsin E is an aspartic proteinase that has been implicated in Ag processing within the class 11 MHC pathway. In this study, we document the presence of cathepsin E message and protein in human myeloid dendritic cells, the preeminent APCs of the immune system. Cathepsin E is found in a perinuclear compartment, which is likely to form part of the endoplasmic reticulum, and also a peripheral compartment just beneath the cell membrane, with a similar distribution to that of Texas Red-dextran within 2 min of endocytosis. To investigate the function of cathepsin E in processing, a new soluble targeted inhibitor was synthesized by linking the microbial aspartic proteinase inhibitor pepstatin to mannosylated BSA via a cleavable disulfide linker. This inhibitor was shown to block cathepsin D/E activity in cell-free assays and within dendritic cells. The inhibitor blocked the ability of dendritic cells from wild-type as well as cathepsin D-deficient mice to present intact OVA, but not an OVA-derived peptide, to cognate T cells. The data therefore support the hypothesis that cathepsin E has an important nonredundant role in the class 11 MHC Ag processing pathway within dendritic cells.