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

Fc gamma receptors (Fc gamma R) 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 Fc gamma Rs, 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-Fc gamma R interaction; one well-described factor is the differential affinity of the six distinct Fc gamma Rs 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 Fc gamma Rs, including asparagine-linked glycosylation. This review also covers the organization of Fc gamma Rs 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.