A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells
A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells
复制标题
DOI：
10.1016/j.immuni.2006.08.017
复制
发表时间：
2006-10-01
期刊：
影响因子：
32.4
通讯作者：
Cresswell, Peter
中科院分区：
文献类型：
--
作者：
Ackerman, Anne L.;Giodini, Alessandra;Cresswell, Peter
树突状细胞向CD8(+) T细胞交叉表达外源抗原（Ags）通常需要它们进入细胞质。在这里，我们发现可溶性和吞噬的细胞外Ags都通过内质网（ER）相关降解（ERAD）所需的分子成分进入细胞质溶胶。外源性铜绿假单胞菌外毒素A抑制蛋白从内质网转运到细胞质，取消了交叉表达。外毒素A还能阻止与抗原加工（TAP）抑制剂相关的转运蛋白ICP47进入细胞质并阻断TAP介导的肽运输。在反转录易位的体外模型中，AAA atp酶p97（一种对ERAD至关重要的酶）是唯一需要从分离的吞噬体输出蛋白质的细胞质辅助因子。交叉表示也需要功能性p97，但不需要常规表示。因此，交叉表达似乎是由于与错误折叠的内质网蛋白降解有关的逆转录易位机制的适应。
Crosspresentation of exogenous antigens (Ags) to CD8(+) T cells by dendritic cells generally requires their entry into the cytosol. Here we show that both soluble and phagocytosed extracellular Ags accessed the cytosol via molecular components required for endoplasmic reticulum (ER)-associated degradation (ERAD). Exogenous Pseudomonas aeruginosa Exotoxin A, which inhibits protein translocation from the ER to the cytosol, abrogated crosspresentation. Exotoxin A also prevented the transporter associated with antigen processing (TAP) inhibitor, ICP47, from entering the cytosol and blocking TAP-mediated peptide transport. In an in vitro model of retrotranslocation, the AAA ATPase p97, an enzyme critical for ERAD, was the only cytosolic cofactor required for protein export from isolated phagosomes. Functional p97 was also required for crosspresentation but not conventional presentation. Thus, crosspresentation appears to result from an adaptation of the retrotranslocation mechanisms involved in the degradation of misfolded ER proteins.