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Review
. 2019 Feb 14:10:223.
doi: 10.3389/fimmu.2019.00223. eCollection 2019.

Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms

Kashyap R Patel  1 , Jacob T Roberts  1 , Adam W Barb  1
Affiliations
Review

Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms

Kashyap R Patel et al. Front Immunol. .

Abstract

Fc γ receptors (FcγR) expressed on the surface of human leukocytes bind clusters of immunoglobulin G (IgG) to induce a variety of responses. Many therapeutic antibodies and vaccine-elicited antibodies prevent or treat infectious diseases, cancers and autoimmune disorders by binding FcγRs, thus there is a need to fully define the variables that impact antibody-induced mechanisms to properly evaluate candidate therapies and design new intervention strategies. A multitude of factors influence the IgG-FcγR interaction; one well-described factor is the differential affinity of the six distinct FcγRs for the four human IgG subclasses. However, there are several other recently described factors that may prove more relevant for disease treatment. This review covers recent reports of several aspects found at the leukocyte membrane or outside the cell that contribute to the cell-based response to antibody-coated targets. One major focus is recent reports covering post-translational modification of the FcγRs, including asparagine-linked glycosylation. This review also covers the organization of FcγRs at the cell surface, and properties of the immune complex. Recent technical advances provide high-resolution measurements of these often-overlooked variables in leukocyte function and immune system activation.

Keywords: ADCC—antibody dependent cellular cytotoxicity; ADCP—antibody dependent cellular phagocytosis; IgG; N-glycosylation; antibody; immune complex; post-translation modification.

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Figures

Figure 1
Figure 1
Multiple variables affect FcγR-mediated immune function. (A) cellular variables influencing FcγR activity that are present before the effector cell engages a target cell. (B) cellular variables influencing FcγR-mediated activity while the effector cell is engaged with a target cell. (C) molecular variables associated with the FcγRs, antibody, and antigen.
Figure 2
Figure 2
Structures and properties of the human Fc γ receptors. Five receptors are expressed in the majority of the population with CD32c expressed only in a small subset. The ribbon diagrams show the structures of the extracellular antibody-binding domains as determined by x-ray crystallography; overlayed black or white circles indicate the sites of N-glycosylation.
Figure 3
Figure 3
N-glycans are processed in the ER and Golgi to produce three major classes: minimally processed oligomannose-type N-glycans, fully processed complex-type N-glycans, and hybrid-type N-glycans with an intermediate level of processing.
See this image and copyright information in PMC

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