Functional Characteristics of the High Affinity IgG Receptor, FcγRI

Abstract

IgG FcRs are important mediators of immunity and play a key role during Ab-based immunotherapy. Within the leukocyte IgG receptor family, only FcγRI is capable of IgG binding with high affinity. FcγRI exists as a complex of a ligand binding α-chain and an FcR γ-chain. The receptors’ α-chain can, furthermore, elicit several functions independent of the ITAM-bearing FcR γ-chain. Functional implications of high-affinity IgG binding and mechanisms underlying FcR γ-chain–independent signaling remain unclear to this day. In this paper, we provide an overview of past literature on FcγRI and address the implications of recently described interactions between cytosolic proteins and the FcγRI α-chain, as well as cytokine-enhanced FcγRI immune complex binding. Furthermore, an analysis of potential polymorphisms within the FCGR1A gene is provided.

CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1‐inducing role of mesenteric lymph node macrophages during colitis

“…However, giving their high MHCII expression, inflammatory M s can potentially present antigens to tissue-resident memory T cells and to the iTreg cells that reach the LP [32,34]. Along that line, due to its high affinity for IgG, the expression of CD64 may possibly arm LP M s with IgG specific for previously encountered pathogens and allow them to efficiently initiate recall responses upon subsequent pathogen reexposure [15]. Although the inflammatory conditions achieved during T cell-mediated colitis do not induce LP M s to migrate to MLNs, it remains possible that some bacterial adjuvants confer MLN-homing property to some LP M s as shown for muscle Mo-DCs [33].…”

“…As a result, upon migration to MLNs they trigger the differentiation of naive CD4 + T cells specific for food and microbiota antigens into induced Foxp3 + regulatory T (iTreg) cells [10][11][12][13]. In contrast, the Int-DCs that develop in inflamed LP upon exposure to pathogens lose their capacity to generate iTreg cells and, upon migration to the MLNs, trigger the differentiation of naive, antigen-responsive CD4 + T cells into T helper type 1 (Th1) cells that are specific for the invading pathogen and produce mainly 14].We have previously reported that the monocyte-derived cells that are present in skeletal muscle express high levels of CD64, the high-affinity IgG receptor FcγR [15]. By using the expression of CD64, we also succeeded in distinguishing M s from DCs in the LP of the large and small intestine and the MLNs of both mice and humans.…”

Human gene copy number variation and infectious disease

“…FcγRI is a high affinity Fcγ receptor for monomeric IgG, with three highly similar genes (>95% 279 identity) assembled in the human reference genome (FCGR1A, FCGR1B and FCGR1C) (Ernst et al 280 1992;Maresco et al 1996;van der Poel et al 2011). The copy number of these genes has increased 281 in the human lineage, and show copy number variation between individuals (Sudmant et al 2010).…”

Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection

“…Antibody-enhanced IL-1␤ Secretion Requires Isotype-specific Antibody-Because Syk is important for antibody-mediated signaling, we sought to verify that mAb 5G22 elevates DENVinduced IL-1␤ due to immune complex formation with the virus.ThisisespeciallyimportantbecauseFc␥RIcanbindmono-meric IgG that is not bound to antigen (74). Thus, we employed an isotype-matched control antibody for side-by-side comparison with mAb 5G22.…”