Imai Jun, Ohashi Sayaka, Sakai Takahiro
Laboratory of Physiological Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan.
Pharmaceutics. 2020 Feb 13;12(2):153. doi: 10.3390/pharmaceutics12020153.
While the success of dendritic cell (DC) vaccination largely depends on cross-presentation (CP) efficiency, the precise molecular mechanism of CP is not yet characterized. Recent research revealed that endoplasmic reticulum (ER)-associated degradation (ERAD), which was first identified as part of the protein quality control system in the ER, plays a pivotal role in the processing of extracellular proteins in CP. The discovery of ERAD-dependent processing strongly suggests that the properties of extracellular antigens are one of the keys to effective DC vaccination, in addition to DC subsets and the maturation of these cells. In this review, we address recent advances in CP, focusing on the molecular mechanisms of the ERAD-dependent processing of extracellular proteins. As ERAD itself and the ERAD-dependent processing in CP share cellular machinery, enhancing the recognition of extracellular proteins, such as the ERAD substrate, by methods may serve to improve the efficacy of DC vaccination.
虽然树突状细胞（DC）疫苗接种的成功很大程度上取决于交叉呈递（CP）效率，但CP的确切分子机制尚未明确。最近的研究表明，内质网（ER）相关降解（ERAD）最初被确定为ER中蛋白质质量控制系统的一部分，在CP中细胞外蛋白质的加工过程中起关键作用。依赖ERAD的加工过程的发现强烈表明，除了DC亚群及其成熟外，细胞外抗原的特性是有效DC疫苗接种的关键之一。在这篇综述中，我们阐述了CP的最新进展，重点关注依赖ERAD的细胞外蛋白质加工的分子机制。由于ERAD本身以及CP中依赖ERAD的加工过程共享细胞机制，通过某些方法增强对细胞外蛋白质（如ERAD底物）的识别可能有助于提高DC疫苗接种的效果。
