Abstract
Antibodies are essential components of an adaptive immune response. Immunoglobulin G (IgG) is the most common type of antibody found in circulation and extracellular fluids. Although IgG alone can directly protect the body from infection through the activities of its antigen binding region, the majority of IgG immune functions are mediated via proteins and receptors expressed by specialized cell subsets that bind to the fragment crystallizable (Fc) region of IgG. Fc gamma (γ) receptors (FcγR) belong to a broad family of proteins that presently include classical membrane-bound surface receptors as well as atypical intracellular receptors and cytoplasmic glycoproteins. Among the atypical FcγRs, the neonatal Fc receptor (FcRn) has increasingly gained notoriety given its intimate influence on IgG biology and its ability to also bind to albumin. FcRn functions as a recycling or transcytosis receptor that is responsible for maintaining IgG and albumin in the circulation, and bidirectionally transporting these two ligands across polarized cellular barriers. More recently, it has been appreciated that FcRn acts as an immune receptor by interacting with and facilitating antigen presentation of peptides derived from IgG immune complexes (IC). Here we review FcRn biology and focus on newer advances including how emerging FcRn-targeted therapies may affect the immune responses to IgG and IgG IC.
Highlights
Immunoglobulin G (IgG) and albumin are the two most abundant serum proteins that possess a long serum half-life owing to their interaction with FcRn, which rescues them from intracellular degradation through a cellular recycling mechanism
Such mechanisms might explain the progressive increase in FcRn expression levels from duodenum to proximal colon [112], as well as the presence of cubilin in human small intestine [128] (Box 4), which would allow for receptor-mediated uptake of albumin similar to processes occurring in the proximal tubules of the kidney [130]
The therapeutic utility in blocking or enhancing albumin-FcRn interactions is less well-explored compared to IgG, largely due to inadequate understanding of albumin biology and pathology, but these studies demonstrate some potential for the albumin-docking site on FcRn as a target for future basic and translational research
Summary
Antibodies are essential components of an adaptive immune response. Fc gamma (γ) receptors (FcγR) belong to a broad family of proteins that presently include classical membrane-bound surface receptors as well as atypical intracellular receptors and cytoplasmic glycoproteins. Among the atypical FcγRs, the neonatal Fc receptor (FcRn) has increasingly gained notoriety given its intimate influence on IgG biology and its ability to bind to albumin. FcRn functions as a recycling or transcytosis receptor that is responsible for maintaining IgG and albumin in the circulation, and bidirectionally transporting these two ligands across polarized cellular barriers. It has been appreciated that FcRn acts as an immune receptor by interacting with and facilitating antigen presentation of peptides derived from IgG immune complexes (IC).
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