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Fc receptors and their interactions with immunoglobulins

Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Annual Review of Cell and Developmental Biology (Impact Factor: 20.24). 02/1996; 12:181-220. DOI: 10.1146/annurev.cellbio.12.1.181
Source: PubMed

ABSTRACT Receptors for the Fc domain of immunoglobulins play an important role in immune defense. There are two well-defined functional classes of mammalian receptors. One class of receptors transports immunoglobulins across epithelial tissues to their main sites of action. This class includes the neonatal Fc receptor (FcRn), which transports immunoglobulin G (IgG), and the polymeric immunoglobulin receptor (pIgR), which transports immunoglobulin A (IgA) and immunoglobulin M (IgM). Another class of receptors present on the surfaces of effector cells triggers various biological responses upon binding antibody-antigen complexes. Of these, the IgG receptors (Fc gamma R) and immunoglobulin E (IgE) receptors (Fc epsilon R) are the best characterized. The biological responses elicited include antibody-dependent, cell-mediated cytotoxicity, phagocytosis, release of inflammatory mediators, and regulation of lymphocyte proliferation and differentiation. We summarize the current knowledge of the structures and functions of FcRn, pIgR, and the Fc gamma R and Fc epsilon RI proteins, concentrating on the interactions of the extracellular portions of these receptors with immunoglobulins.

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    • "FcRn is located primarily intracellularly within the endolysosomal system of APC and less so on the cell surface where it could theoretically compete for IgG binding with FcγR (76). The critical binding site for FcRn on the IgG Fc region involves the I253, H310, and H435 residues within the CH2:CH3 domains of IgG Fc and is distinct from where FcγR binding to IgG occurs (77–84). In contrast to FcγRs, binding is entirely independent of IgG glycosylation. "
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    • "We know that orthologs of IgG first appeared in the common mammalian ancestor because monotremes have them (14). The neonatal Fc receptor (FCGRT), however, which is the gene that enables the crucial transfer of IgG from mother to offspring as well prolonging the beneficial effects of IgG by increasing its half-life (40), is only present in marsupial and placental genomes. Studies of human infant mortality to most common infections show an exponential decline with the age (4) with exception of the first year of life where transfer of maternal IgG plays a crucial role in infant survival through protective immunity. "
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