Elsevier

Current Opinion in Immunology

Volume 72, October 2021, Pages 126-134
Current Opinion in Immunology

Membrane cofactor protein (MCP; CD46): deficiency states and pathogen connections

https://doi.org/10.1016/j.coi.2021.04.005Get rights and content

Highlights

  • Membrane cofactor protein (MCP; CD46) protects host cells from complement attack.

  • Rare variants leading to haploinsufficiency predispose to renal disease.

  • Subversion by six bacteria and five viruses (‘pathogen magnet’).

  • Role in therapeutics against COVID-19 and cancer.

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.

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