Complement receptor 1, 2, and 3 (CR1/2/3)

Complement receptor 1/2/3 refers to a collective group of three distinct cell-surface proteins—CR1 (CD35), CR2 (CD21), and CR3 (CD11b/CD18)—that play essential roles in the regulation and effector functions of the complement system [1, 8]. Complement receptor 1 is primarily responsible for clearing C3b/C4b-opsonized immune complexes and acts as a regulator of the complement cascade by inhibiting C3 and C5 convertases [2, 14]. Complement receptor 2 serves as a critical co-receptor on B cells, binding to C3d fragments to lower the threshold for B cell activation and linking innate and adaptive immune responses [6, 15]. Complement receptor 3, also known as Mac-1, is a beta-2 integrin expressed on myeloid cells that mediates the phagocytosis of iC3b-coated pathogens and facilitates leukocyte adhesion to the endothelium [2, 9]. These receptors are significant therapeutic targets in various conditions, including systemic lupus erythematosus, rheumatoid arthritis, and Alzheimer's disease [3, 6, 7]. Pharmacological modulation of these receptors, such as the use of soluble CR1 (e.g., TP10, Mirococept), is being explored to reduce tissue damage in inflammatory diseases and to improve the delivery of gene therapy vectors by preventing their phagocytic clearance [4, 14].

Other names

CR1 (CD35)CR2 (CD21)CR3 (CD11b/CD18)Mac-1C3b/C4b receptorC3d receptorIntegrin alpha-M beta-2Regulators of complement activation (RCA)

Inhibition of C3 and C5 convertases and promotion of C3b/C4b degradation (CR1); modulation of B cell receptor signaling thresholds (CR2); and blockade of iC3b-mediated phagocytosis and leukocyte endothelial adhesion (CR3) [2, 9, 14, 15].