科學家揭示受體DNGR-1的功能

科學家揭示受體DNGR-1的功能

作者：

小柯機器人

發布時間：2020/12/22 22:07:09

英國弗朗西斯·克裡克研究所Caetano Reis e Sousa小組取得一項新突破。他們的研究發現受體DNGR-1誘導的吞噬體破裂信號促進了與死細胞相關的抗原交叉呈遞。相關論文於2020年12月21號發表於國際學術期刊《自然-免疫學》雜誌。

研究人員發現DNGR-1是XP專一性受體，在與配體結合後誘發促進吞噬體破裂的信號。這有利於吞噬體內容物逃逸到細胞質中，在細胞質內它們經歷了內源性I類主要組織相容性抗原複合物加工途徑。DNGR-1的活性映射到其信號結構域，即使將其剪接成異源受體並在異源細胞中表達，它也會激活SYK和NADPH氧化酶從而完成對吞噬體的破壞。該研究數據揭示了先天性免疫受體的存在，該受體與配體結合導致內吞小泡破裂，從而允許MHC I類抗原呈遞外源抗原並調節適應性免疫。

研究人員表示，常規1型樹突狀細胞（cDC1）負責將許多病毒和腫瘤抗原交叉呈遞至CD8+ T細胞。DNGR-1（也稱為CLEC9A）高表達可用於分離小鼠和人體中的cDC1細胞，DNGR-1是一種結合死細胞碎片並促進細胞碎片相關抗原XP的受體。

附：英文原文

Title: The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens

Author: Johnathan Canton, Hanna Blees, Conor M. Henry, Michael D. Buck, Oliver Schulz, Neil C. Rogers, Eleanor Childs, Santiago Zelenay, Hefin Rhys, Marie-Charlotte Domart, Lucy Collinson, Andres Alloatti, Cara J. Ellison, Sebastian Amigorena, Venizelos Papayannopoulos, David C. Thomas, Felix Randow, Caetano Reis e Sousa

Issue&Volume: 2020-12-21

Abstract: Type 1 conventional dendritic (cDC1) cells are necessary for cross-presentation of many viral and tumor antigens to CD8+ T cells. cDC1 cells can be identified in mice and humans by high expression of DNGR-1 (also known as CLEC9A), a receptor that binds dead-cell debris and facilitates XP of corpse-associated antigens. Here, we show that DNGR-1 is a dedicated XP receptor that signals upon ligand engagement to promote phagosomal rupture. This allows escape of phagosomal contents into the cytosol, where they access the endogenous major histocompatibility complex class I antigen processing pathway. The activity of DNGR-1 maps to its signaling domain, which activates SYK and NADPH oxidase to cause phagosomal damage even when spliced into a heterologous receptor and expressed in heterologous cells. Our data reveal the existence of innate immune receptors that couple ligand binding to endocytic vesicle damage to permit MHC class I antigen presentation of exogenous antigens and to regulate adaptive immunity. 

DOI: 10.1038/s41590-020-00824-x

Source: https://www.nature.com/articles/s41590-020-00824-x