Abstract
IgG antibodies are the basis of some of the most effective therapeutics developed over the last 20 years. These antibodies are highly specific, have long serum-half lives, and can be produced relatively routinely, making them ideal drugs for immunotherapy. The degree of regulation on IgG antibody effector functions by the composition of the single, N-linked glycan attached to the Fc is increasingly appreciated. IgG antibodies with identical protein sequences can gain a 50-fold potency, in terms of initiating antibody-dependent cellular cytotoxicity (ADCC) by removal of the single fucose residue from the Fc glycan. Conversely, the addition of sialic acid to the terminus of the Fc glycan converts IgG antibodies into anti-inflammatory mediators, capable of suppressing autoantibody driven inflammation. This review will discuss the contribution of the Fc glycan to IgG antibody effector functions, the regulation of the antibody glycosylation in vivo, implications for the rational design of IgG antibody-based therapeutics, and touch upon the contribution of glycosylation to other immunoglobulin isotypes.
Highlights
Antibodies play key roles in humoral adaptive immune response by binding to specific antigens and linking them to the innate immune system
IgG can activate leukocytes by binding to activating Fc γ receptors (FcγRs) (FcγRIA, FcγRIIA, FcγRIIC, and FcγRIIIA) that typically signal through an immunoreceptor tyrosine-based activation motif (ITAM)
Regardless of the expression systems, afucosylated IgG exhibited a marked increase in binding affinity to human FcγRIIIA, NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), and antiviral activity measured by antibody-dependent cell-mediated virus inhibition (ADCVI) assays [40,41]
Summary
Antibodies play key roles in humoral adaptive immune response by binding to specific antigens and linking them to the innate immune system. Antibodies are comprised of basic structural units of two identical heavy and two identical light polypeptide chains. These chains are linked by disulfide bonds forming a “Y”-shaped structure [8]. The most abundant class with longest half-life is IgG comprising 75% of antibodies in circulation. IgE is the least abundant in the circulation (
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