Low affinity immunoglobulin gamma Fc receptor III-alpha (FCGR3A)

The Low affinity immunoglobulin gamma Fc receptor III-alpha (CD16a) is a crucial transmembrane glycoprotein expressed on natural killer (NK) cells, monocytes, and macrophages [1]. It functions as a key mediator of the innate immune response by binding to the Fc portion of IgG1 and IgG3 antibodies that have coated target cells [2]. This binding event triggers antibody-dependent cellular cytotoxicity (ADCC), leading to the release of cytotoxic granules and the subsequent lysis of the target cell [3]. In the pharmaceutical industry, CD16a is a vital target for therapeutic monoclonal antibodies, such as rituximab and trastuzumab, which rely on the receptor to recruit immune cells to destroy tumor cells [4]. A well-known genetic variation, the V158F polymorphism, significantly affects the binding affinity of the receptor for IgG, thereby influencing the clinical efficacy of many antibody-based treatments [5]. Beyond oncology, CD16a is involved in the clearance of immune complexes and the pathogenesis of autoimmune diseases like systemic lupus erythematosus [1][6]. Modern drug development efforts often utilize Fc-engineering to increase the affinity of antibodies for CD16a to enhance therapeutic potency [7]. However, potent activation of this pathway must be carefully managed to avoid systemic safety issues such as cytokine release syndrome [8].

Other names

CD16aFc gamma receptor IIIaCD16A antigenFCG3FCGR3IGFR3FcR-10IgG Fc receptor III-2

Binds to the Fc region of IgG antibodies (primarily IgG1 and IgG3) to bridge adaptive and innate immunity, triggering antibody-dependent cellular cytotoxicity (ADCC) and effector cell activation.