Low affinity immunoglobulin gamma Fc region receptor II-a and II-c (FcγRIIA and FcγRIIC)

FcγRIIA (FCGR2A) and FcγRIIC (FCGR2C) are low-affinity activating receptors for the Fc region of immunoglobulin G (IgG), belonging to the CD32 family [1, 3, 19]. FcγRIIA is widely expressed on myeloid cells, including monocytes, macrophages, neutrophils, and platelets, where it plays a central role in the phagocytosis of opsonized pathogens and the clearance of immune complexes [2, 12, 15, 21]. FcγRIIC is a chimeric receptor resulting from gene recombination, primarily expressed on natural killer (NK) cells and neutrophils in a subset of the population [3, 12, 13]. Both receptors possess an immunoreceptor tyrosine-based activation motif (ITAM) in their cytoplasmic domains, which initiates pro-inflammatory signaling upon receptor cross-linking [3, 4, 10, 12]. These receptors are critical determinants of the efficacy of therapeutic monoclonal antibodies, as they mediate antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) [6, 15, 16, 18]. Genetic variations, particularly the FCGR2A H131R polymorphism and the FCGR2C open reading frame (ORF) variant, are linked to susceptibility to autoimmune diseases like systemic lupus erythematosus and idiopathic thrombocytopenic purpura, as well as to the clinical response to cancer immunotherapies [7, 13, 14, 19, 22].

Other names

CD32CD32aCD32cFCGR2AFCGR2CFcRII-aFcRII-cFc gamma receptor IIaFc gamma receptor IIcFc fragment of IgG receptor IIaFc fragment of IgG receptor IIc

These receptors are activating IgG receptors that signal through an immunoreceptor tyrosine-based activation motif (ITAM) in their cytoplasmic tails. Upon cross-linking by the Fc region of IgG antibodies or immune complexes, they trigger downstream signaling pathways (e.g., Syk kinase activation) that lead to effector functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and the release of inflammatory mediators.