Low affinity immunoglobulin gamma Fc receptor II-a (FCGR2A)

Low affinity immunoglobulin gamma Fc receptor II-a (FCGR2A), also known as CD32a, is a crucial cell surface glycoprotein expressed on various myeloid cells, including macrophages, neutrophils, and platelets (UniProt: P12318). It functions as an activating receptor that binds the Fc portion of IgG antibodies, particularly when they are part of immune complexes, thereby triggering phagocytosis and the release of inflammatory mediators (NCBI Gene: 2212). In the context of hematology, FCGR2A is the only Fc receptor present on platelets and is the primary mediator of platelet activation in heparin-induced thrombocytopenia (HIT) (PubMed: 26133345). The receptor's affinity for IgG is significantly influenced by a common genetic polymorphism, H131R, where the histidine variant (H131) shows higher affinity for IgG2 than the arginine variant (R131) (PubMed: 15585480). This polymorphism is a known determinant of clinical response to various therapeutic monoclonal antibodies used in oncology and autoimmune treatment. Furthermore, FCGR2A is essential for the efficacy of many antibody-based therapies by facilitating antibody-dependent cellular cytotoxicity (ADCC) and the clearance of opsonized targets (PubMed: 18491692).

Other names

CD32aFc-gamma RII-aFCG2FCGR2CD32 antigenIgG Fc receptor II-aFCGR2A1

Binding of the Fc portion of IgG antibodies or immune complexes to the extracellular domain of the receptor triggers phosphorylation of the intracellular Immunoreceptor Tyrosine-based Activation Motif (ITAM) by Src family kinases (e.g., Lyn, Fyn), leading to the recruitment of Syk kinases and subsequent cellular activation (UniProt: P12318; PubMed: 18491692).