A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function. (6th September 2019)

• Record Type: Journal Article
• Authors: Yamaguchi, Yoshiki; Barb, Adam W
• Is Part Of: Glycobiology. Volume 30:Number 4(2020)
• Page Start: 214
• Page End: 225
• Publication Date: 2019-09-06
• Subjects: antibody -- Fc gamma receptor -- immunoglobulin G -- N-glycosylation; Glycoproteins -- Periodicals; Glycolipids -- Periodicals; Glycoconjugates -- Periodicals; 572.567
• DOI: 10.1093/glycob/cwz068
• Languages: English
• ISSNs: 0959-6658

Abstract

Abstract: Therapeutic monoclonal antibodies (mAbs) are the fastest growing group of drugs with 11 new antibodies or antibody-drug conjugates approved by the Food and Drug Administration in 2018. Many mAbs require effector function for efficacy, including antibody-dependent cell-mediated cytotoxicity triggered following contact of an immunoglobulin G (IgG)-coated particle with activating crystallizable fragment (Fc) γ receptors (FcγRs) expressed by leukocytes. Interactions between IgG1 and the FcγRs require post-translational modification of the Fc with an asparagine-linked carbohydrate (N-glycan). Though the structure of IgG1 Fc and the role of Fc N-glycan composition on disease were known for decades, the underlying mechanism of how the N-glycan affected FcγR binding was not defined until recently. This review will describe the current understanding of how N-glycosylation impacts the structure and function of the IgG1 Fc and describe new techniques that are poised to provide the next critical breakthroughs.