Low affinity immunoglobulin gamma Fc receptor III-A (CD16a) (FcγRIIIa)

The FcγRIIIa – antibody Fc interface represents the structural and functional contact area between the Fc region of an IgG antibody and the Low affinity immunoglobulin gamma Fc receptor III-A (CD16a). This receptor is predominantly expressed on natural killer (NK) cells and certain monocytes/macrophages, acting as a bridge between the adaptive and innate immune systems [1, 2]. Upon binding of an antibody-coated target cell, the engagement of FcγRIIIa triggers antibody-dependent cellular cytotoxicity (ADCC), leading to the release of cytotoxic granules that induce target cell lysis [2]. This interface is a pivotal target in oncology, where therapeutic monoclonal antibodies like Rituximab and Trastuzumab utilize it to recruit immune effector cells against tumors [3]. Modern drug development often involves Fc-engineering, such as afucosylation or specific amino acid substitutions (e.g., Margetuximab), to increase binding affinity to FcγRIIIa and overcome the lower affinity associated with certain genetic variants [3, 4]. Clinical efficacy of many antibodies is significantly influenced by the FCGR3A V158F polymorphism, which dictates the baseline binding strength of the Fc-receptor interaction [4].

Other names

CD16aFCGR3AFc-gamma RIIIaIgG Fc receptor III-ACD16A antigenFc fragment of IgG receptor IIIa

Enhancement of antibody-dependent cellular cytotoxicity (ADCC) through optimized Fc-receptor binding and recruitment of effector cells.