FcγRs in Health and Disease

Abstract

Genetic defects affecting the humoral immune response and especially the production of antibodies of the immunoglobulin G (IgG) isotype result in a heightened susceptibility to infections. Studies over the last years have demonstrated the crucial role of Fc-receptors for IgG (FcγRs) widely expressed on innate immune effector cells in mediating the protective function of IgG. During the last years, additional ligands interacting with FcγRs as well as additional receptors binding to IgG glycosylation variants have been identified. In this review, we discuss how the interaction of these different ligands with classical and novel Fcγ-receptors influences the immune response and which strategies microorganisms have developed to prevent them.

FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial

“…FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial Shuying S. Li, 1 Peter B. Gilbert, 1 Georgia D. Tomaras, 2 Gustavo Kijak, 3 Guido Ferrari, 2 Rasmi Thomas, 3 Chul-Woo Pyo, 4 Susan Zolla-Pazner, 5 David Montefiori, 2 Hua-Xin Liao, 2 Gary Nabel, 6 Abraham Pinter, 7 David T. Evans, 8 Raphael Gottardo, 1 James Y. Dai, 1 Holly Janes, 1 Daryl Morris, 1 Youyi Fong, 1 Paul T. Edlefsen, 1 Fusheng Li, cantly associated with VE, the SNPs that were captured by the tag SNP (correlated with r 2 ≥ 0.8) would be evaluated, and the tag SNP and captured SNPs would be annotated for interpretations.…”

LILR-B1 blocks activating FcγR signaling to allow antibody dependent enhancement of dengue virus infection

“…Apart from inducing pathogen destruction via degradation in endosomal and lysosomal vesicles, activating signaling pathways triggered upon binding of immune complexes to cellular FcγRs result in cell activation and the release of proinflammatory cytokines (9)(10)(11). With respect to cell-autonomous antiviral responses, a set of genes, which are also triggered by type I interferons and hence are called IFN-stimulated genes (ISG), can be induced via signaling through activating FcγRs and result in inhibition of virus replication.…”

“…Of note, such a system has to be tightly regulated to prevent an unwanted shut-down of cell physiology by innocuous antigens and small amounts of immune complexes present in the blood at all times. Such a threshold may be established by the coexpression of activating and inhibitory FcγRs on the surface of most innate immune cells (10,12). On a molecular level this threshold is established via the simultaneous phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the cytosolic domain of FcγRIIB and the recruitment of SHP-1, which blocks downstream signaling pathways initiated by activating FcγRs via the spleen tyrosine kinase (Syk) (13,14).…”

Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcγ receptor engagement

“…The IgG Fc receptors (FcγRs) have emerged as central determinants of the in vivo function of IgG antibodies for such diverse activities as cytotoxicity, virus and toxin neutralization, immunomodulation, and anti-inflammatory responses (19,20). In both mouse and human, the FcγR system comprises several immunoreceptor tyrosine-based activation motif-containing activating FcγRs (FcγRI, FcγRIII, and FcγRIV in mouse; huFcγRI, huFcγRIIA, and huFcγRIIIA in human) and one immunoreceptor tyrosine-based inhibitory motif-containing inhibitory FcγR (FcγRIIB in mouse and huFcγRIIB in human).…”