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

Low affinity immunoglobulin gamma Fc receptor II-a (FcγRIIA), also known as CD32a, is a cell surface glycoprotein that plays a critical role in the immune system by bridging the humoral and cellular immune responses [UniProt, P12318]. It is primarily expressed on myeloid cells, including macrophages, neutrophils, and monocytes, as well as on platelets [PubMed, PMID: 18448454]. Unlike other Fc receptors, FcγRIIA contains an intrinsic immunoreceptor tyrosine-based activation motif (ITAM) within its cytoplasmic domain, allowing it to directly initiate activating signals upon binding to the Fc region of IgG antibodies [NCBI Gene, 2212]. This interaction triggers essential processes such as phagocytosis, the release of inflammatory mediators, and platelet aggregation [StatPearls, Physiology, Fc Receptors]. In disease contexts, FcγRIIA is implicated in the pathogenesis of autoimmune disorders like systemic lupus erythematosus (SLE) and immune thrombocytopenic purpura (ITP), where it mediates the clearance of autoantibody-coated cells [PubMed, PMID: 26139160]. It is also a key player in heparin-induced thrombocytopenia (HIT), where immune complexes activate platelets via this receptor [PubMed, PMID: 23047714]. Therapeutic strategies involve modulating FcγRIIA activity through monoclonal antibodies, Fc-engineered proteins, or downstream signaling inhibitors to either enhance anti-tumor activity or suppress harmful inflammatory responses [Journal of Clinical Investigation, 2015].

Other names

CD32aCD32FCGR2AFc-gamma RII-aFCG2IGFR2Low affinity immunoglobulin gamma Fc receptor II-a

Binding to the Fc portion of IgG antibodies leads to the phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) by Src family kinases (e.g., Lyn), which recruits and activates Syk kinase, triggering downstream calcium signaling and cellular activation [UniProt, P12318; PubMed, PMID: 18448454].