Division of Rheumatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Curr Opin Immunol. 2021 Oct;72:126-134. doi: 10.1016/j.coi.2021.04.005. Epub 2021 May 15.
Membrane cofactor protein (MCP; CD46), a ubiquitously expressed complement regulatory protein, serves as a cofactor for serine protease factor I to cleave and inactivate C3b and C4b deposited on host cells. However, CD46 also plays roles in human reproduction, autophagy, modulating T cell activation and effector functions and is a member of the newly identified intracellular complement system (complosome). CD46 also is a receptor for 11 pathogens ('pathogen magnet'). While CD46 deficiencies contribute to inflammatory disorders, its overexpression in cancers and role as a receptor for some adenoviruses has led to its targeting by oncolytic agents and adenoviral-based therapeutic vectors, including coronavirus disease of 2019 (COVID-19) vaccines. This review focuses on recent advances in identifying disease-causing CD46 variants and its pathogen connections.
膜辅因子蛋白 (MCP; CD46)，一种广泛表达的补体调控蛋白，作为丝氨酸蛋白酶因子 I 的辅助因子，可切割并灭活沉积在宿主细胞上的 C3b 和 C4b。然而，CD46 也在人类生殖、自噬、调节 T 细胞激活和效应功能中发挥作用，是新发现的细胞内补体系统 (complosome) 的成员。CD46 也是 11 种病原体的受体（“病原体磁铁”）。虽然 CD46 缺乏会导致炎症性疾病，但它在癌症中的过度表达以及作为某些腺病毒受体的作用，导致其成为溶瘤剂和基于腺病毒的治疗载体的靶点，包括 2019 年冠状病毒病 (COVID-19) 疫苗。本综述重点介绍了鉴定致病 CD46 变体及其与病原体关联的最新进展。
