The Role Of Igg Fc N-Glycosylation In Antibody-Dependent Cell-Mediated Cytotoxicity (Adcc)

N-glycosylation of immunoglobulin G (IgG) is essential for effector functions of the antibody, including antibody-dependent cell-mediated cytotoxicity (ADCC). IgG, produced by plasma cells, consists of two heavy and two light chains. Two fragments Fab and Fc are distinguished in IgG structure. The Fab fragment recognizes antigens while the Fc fragment is responsible for an activation of effector cells. Each heavy chain of IgG contains one evolutionary conserved N-glycosylation site at the asparagine 297 located in the hinge region. The Fab fragment is also glycosylated in 15-25% of IgG molecules. N-oligosaccharides of both Fc and Fab have a biantennary complex-type structure. The presence of sugar residues in IgG determines the proper conformation of the molecule. The monosaccharide composition of N-glycans regulates IgG effector functions by affecting the Fc binding to the effector cells. In the humoral immune response, IgG through the Fab fragment recognizes foreign antigens, whereas Fc binds to its receptor on effector cells, initiating a cytotoxic effect against the recognized antigen, among other in ADCC process. N-glycans of Fc fragment are involved in IgG interaction with FcR receptor. Core fucosylation of Fc N-glycans reduces antibody binding to Fe gamma RIIIa and attenuates cytotoxic response. In turn IgG defucosylation significantly increases the cytotoxic effect. Sialylation of N-glycans induces an anti-inflammatory response while the presence of agalactosylated IgG forms is an indicator of ongoing inflammation. The profile of Fc IgG glycosylation reflects the effector functions of antibodies, including their cytotoxic activity in ADCC process. Therefore the modification of sugar composition is crucial to achieve the desired therapeutic efficacy of antibodies used mainly in cancer therapy.