Fc gamma receptor I and Fc gamma receptor IIIa (FcγRI (CD64) and FcγRIIIa (CD16a))

Fc gamma receptor I (FcγRI, CD64) and Fc gamma receptor IIIa (FcγRIIIa, CD16a) are transmembrane glycoproteins of the immunoglobulin superfamily that bind the Fc region of IgG antibodies to link humoral and cellular immunity. FcγRI is the only high-affinity FcγR for monomeric IgG and is predominantly expressed on macrophages, monocytes, and dendritic cells, mediating phagocytosis, antigen presentation, and cytokine production through ITAM-dependent signaling[1][3][4]. FcγRIIIa is expressed principally on natural killer (NK) cells and mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and inflammatory signaling. Both receptors convey signals via immunoreceptor tyrosine-based activation motifs (ITAMs), either intrinsically or through the common gamma chain adaptor protein, and play critical roles in the efficacy of IgG-based therapeutics by engaging immune effector functions. Their activity is modulated by allelic polymorphisms, glycosylation states, and receptor density, significantly influencing clinical response and safety profiles for monoclonal antibody treatments[2][3][6][7].

Other names

CD64High affinity IgG receptorCD16aLow affinity IgG receptorNK cell Fc receptor

Antibody-dependent cellular cytotoxicity (ADCC): FcγRIIIa on NK cells engages IgG coated on target cells, leading to lysis. Antibody-dependent cellular phagocytosis (ADCP): FcγRI/IIIa on phagocytes promotes uptake and destruction of IgG-opsonized targets. Cytokine release and immune cell activation via ITAM motif signaling cascade (Src family kinases → Syk → downstream pathways).