Low affinity immunoglobulin gamma Fc receptor IIa (FCGR2A)

Low affinity immunoglobulin gamma Fc receptor IIa (FCGR2A), also known as CD32a, is a critical cell-surface glycoprotein that bridges the humoral and cellular immune systems by recognizing the Fc portion of IgG antibodies [UniProt: P12318]. It is widely expressed on myeloid cells, including macrophages, neutrophils, and monocytes, where it serves as an activating receptor to initiate phagocytosis and the production of inflammatory mediators [NCBI: 2212]. Notably, it is the only Fc receptor expressed on human platelets, making it the central mediator of platelet activation and thrombosis in conditions like Heparin-Induced Thrombocytopenia (HIT) [PMID: 28624792]. The receptor's function is significantly influenced by a common genetic polymorphism (H131R), which alters its binding affinity for IgG2 and modulates susceptibility to autoimmune and infectious diseases [PMID: 15507111]. In drug development, CD32a is a key target for Fc-engineering strategies aimed at enhancing the antibody-dependent cellular phagocytosis (ADCP) of therapeutic monoclonal antibodies used in oncology [PMID: 25292418]. Furthermore, high-dose intravenous immunoglobulin (IVIG) therapy acts partly by saturating these receptors to suppress pathological immune responses.

Other names

CD32aCDw32Fc-gamma RII-aFCG2Fc receptor gamma-chain IIaFc-gamma receptor IIA

The receptor binds the Fc region of IgG antibodies (specifically IgG1 and IgG2) present in immune complexes, leading to the phosphorylation of its internal immunoreceptor tyrosine-based activation motif (ITAM) by Src family kinases; this recruits Syk kinases to trigger phagocytosis, respiratory burst, and cytokine release [UniProt: P12318] [PMID: 25292418].