期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：23
页码：7237-7242
DOI：10.1073/pnas.1505924112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceDendritic cells are critical in regulating immune responses. DEC205 (CD205) is an endocytotic receptor on dendritic cells with antigen presentation function and has been widely used in immune therapies. Here, we report that DEC205 is an immune receptor that recognizes apoptotic and necrotic cells specifically through a pH-dependent mechanism. The ectodomain of DEC205 forms a double-ringed conformation at acidic pH and becomes extended at basic pH. DEC205 only recognizes apoptotic and necrotic cells at acidic conditions with its N-terminal small ring and has no binding activities to healthy cells at either acidic or basic conditions, thus representing a novel pathway for immune clearance of dead cells and a potential mechanism for tumor scavenging. Dendritic cells play important roles in regulating innate and adaptive immune responses. DEC205 (CD205) is one of the major endocytotic receptors on dendritic cells and has been widely used for vaccine generation against viruses and tumors. However, little is known about its structure and functional mechanism. Here we determine the structure of the human DEC205 ectodomain by cryoelectron microscopy. The structure shows that the 12 extracellular domains form a compact double ring-shaped conformation at acidic pH and become extended at basic pH. Biochemical data indicate that the pH-dependent conformational change of DEC205 is correlated with ligand binding and release. DEC205 only binds to apoptotic and necrotic cells at acidic pH, whereas live cells cannot be recognized by DEC205 at either acidic or basic conditions. These results suggest that DEC205 is an immune receptor that recognizes apoptotic and necrotic cells specifically through a pH-dependent mechanism.
