Complement receptor type 2 (CR2) (CR2)

Complement receptor type 2 (CR2), also known as CD21, is a type I transmembrane glycoprotein primarily expressed on mature B cells and follicular dendritic cells [4, 16]. It serves as a critical link between innate and adaptive immunity by acting as a co-receptor for the B-cell receptor (BCR) complex, significantly lowering the threshold for B-cell activation when binding to C3d-opsonized antigens [8, 13]. Beyond its role in the complement system, CR2 is the primary receptor for the Epstein-Barr virus (EBV), facilitating viral entry into B cells [4, 11]. In therapeutic development, CR2 is frequently utilized as a targeting moiety in fusion proteins, such as TT30, to deliver complement inhibitors specifically to sites of tissue injury where C3d is deposited [2, 21]. This site-specific approach aims to treat conditions like lupus nephritis and paroxysmal nocturnal hemoglobinuria while minimizing systemic immunosuppression [1, 21]. Dysregulation of CR2 is associated with various conditions, including systemic lupus erythematosus (SLE), where reduced expression is observed, and B-cell malignancies [6, 14].

Other names

CD21C3d receptorEpstein-Barr virus receptorComplement component (3d/Epstein Barr Virus) receptor 2C3DRSLEB9

CR2-based fusion proteins act as site-specific complement inhibitors by using the CR2 domain to target C3d-coated tissues, where the linked effector domain (e.g., Factor H or CR1) suppresses further complement activation [1, 2, 21]. Additionally, CR2 can be targeted to modulate B-cell signaling or block viral entry [12].