泛素
泛素连接酶
细胞生物学
CD86
主要组织相容性复合体
抗原呈递
生物
免疫系统
遗传学
T细胞
基因
作者
Haiyin Liu,Kayla R Wilson,A Firth,Christophe Macri,Patrick Schriek,Annabelle B Blum,Javiera Villar,Samuel Wormald,Mitch Shambrook,Bangyan Xu,Hui Jing Lim,Hamish E G McWilliam,Andrew F. Hill,Laura E. Edgington-Mitchell,Irina Caminschi,Mireille H. Lahoud,Élodie Segura,Marco J. Herold,José A Villadangos,Justine D. Mintern
标识
DOI:10.1038/s41467-022-29524-w
摘要
The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses.
科研通智能强力驱动
Strongly Powered by AbleSci AI