CD16a

CD16a, also known as Fc gamma receptor IIIA (FcγRIIIa), is a receptor for the Fc portion of IgG antibodies and a key mediator of antibody-dependent cellular cytotoxicity (ADCC). In humans, FCGR3A encodes CD16a on chromosome 1. The receptor is expressed primarily on natural killer (NK) cells, with additional expression on certain T cell subsets and on monocytes, macrophages, and dendritic cells.

CD16a is a transmembrane glycoprotein that pairs with signaling adaptor proteins containing immunoreceptor tyrosine-based activation motifs (ITAMs), typically the FcεRIγ chain or the FcRζ chain. This association completes the signaling complex required to trigger cytotoxic responses. The ligand-binding domain recognizes the Fc region of IgG, with higher affinity for IgG1 and IgG3 than for other subclasses. A common polymorphism (V158F) in FCGR3A alters affinity for IgG1/IgG3, with the V158 variant displaying stronger binding and greater ADCC activity in several assays.

Expression of CD16a enables immune effector functions such as NK cell–mediated lysis of antibody-coated target cells and the production of cytokines that modulate the immune response. The level and distribution of CD16a can influence the effectiveness of monoclonal antibody therapies that rely on ADCC, including rituximab, cetuximab, and trastuzumab. Therapeutic antibodies engineered to enhance CD16a engagement, such as afucosylated variants, aim to increase ADCC and clinical efficacy.