Antibody receptors steal the sweet spotlight

Abstract

Immunoglobulin G (IgG) antibodies function, in part, through ligation of cell-surface Fc receptors such as FcγRIIIA (also known as CD16A). IgG glycosylation is known to impact antibody function, but the role of FcγRIIIA glycans, if any, is unclear. Patel et al. now reveal that these glycans do impact protein conformation and IgG affinity and display cell-specific glycosylation patterns, leading to a potential model in which the affinity and possibly function of Fc receptors is dictated by the cell type and its surface glycome.

Figure 1.

Together with the γ2 chain, FcγRIIIA recognizes and binds to the Fc domain of IgG to initiate cellular activation signals. Patel et al. (6) have discovered that the glycans on FcγRIIIA from primary and uncultured NK cells from human donors carry a much higher proportion of high mannose and hybrid N-glycans than recombinant FcγRIIIA expressed by HEK293 cells in culture. HEK293 cells preferentially placed complex-type N-glycans on the receptor, which cause a different conformational change from the NK-mediated glycans and a 12-fold reduction in binding affinity (K_d) for IgG. These findings suggest that FcγR-mediated cell signaling and overall response to IgG stimulation may depend on the cell-surface glycome.