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FcRn: From Molecular Interactions to Regulation of IgG Pharmacokinetics and Functions

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Fc Receptors

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 382))

Abstract

The neonatal Fc receptor, FcRn, is related to MHC class I with respect to its structure and association with β2microglobulin (β2m). However, by contrast with MHC class I molecules, FcRn does not bind to peptides, but interacts with the Fc portion of IgGs and belongs to the Fc receptor family. Unlike the ‘classical’ Fc receptors, however, the primary functions of FcRn include salvage of IgG (and albumin) from lysosomal degradation through the recycling and transcytosis of IgG within cells. The characteristic feature of FcRn is pH-dependent binding to IgG, with relatively strong binding at acidic pH (<6.5) and negligible binding at physiological pH (7.3–7.4). FcRn is expressed in many different cell types, and endothelial and hematopoietic cells are the dominant cell types involved in IgG homeostasis in vivo. FcRn also delivers IgG across cellular barriers to sites of pathogen encounter and consequently plays a role in protection against infections, in addition to regulating renal filtration and immune complex-mediated antigen presentation. Further, FcRn has been targeted to develop both IgGs with extended half-lives and FcRn inhibitors that can lower endogenous antibody levels. These approaches have implications for the development of longer lived therapeutics and the removal of pathogenic or deleterious antibodies.

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Abbreviations

APCs:

Antigen presenting cells

BBB:

Blood–brain barrier

CNS:

Central nervous system

DCs:

Dendritic cells

ECs:

Endothelial cells

FcRn:

Neonatal Fc receptor

GBM:

Glomerular basement membrane

HCs:

Hematopoietic cells

HIV:

Human immunodeficiency virus

HSV:

Herpes simplex virus

ICs:

Immune complexes

Ig:

Immunoglobulin

IVIG:

Intravenous immunoglobulin

KO:

Knockout

LP:

Lamina propria

mAbs:

Monoclonal antibodies

MALT:

Mucosa-associated lymphoid tissue

MHC:

Major histocompatibility

MLNs:

Mesenteric lymph nodes

Myo Vb:

Motor myosin Vb

OVA:

Ovalbumin

PCT:

Proximal convoluted tubule

β2m:

β2microglobulin

TC:

Transport carrier

TLR:

Toll-like receptor

WT:

Wildtype

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Authors and Affiliations

  1. Department of Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX, 75390, USA

    Dilip K. Challa, Ramraj Velmurugan, Raimund J. Ober & E. Sally Ward

  2. Department of Electrical Engineering, University of Texas at Dallas, Richardson, TX, 75080, USA

    Raimund J. Ober

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  1. Dilip K. Challa
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  2. Ramraj Velmurugan
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  3. Raimund J. Ober
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  4. E. Sally Ward
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Correspondence to E. Sally Ward .

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  1. Institut Pasteur, Paris, France

    Marc Daeron

  2. Department of Biology, Institute of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany

    Falk Nimmerjahn

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Challa, D.K., Velmurugan, R., Ober, R.J., Sally Ward, E. (2014). FcRn: From Molecular Interactions to Regulation of IgG Pharmacokinetics and Functions. In: Daeron, M., Nimmerjahn, F. (eds) Fc Receptors. Current Topics in Microbiology and Immunology, vol 382. Springer, Cham. https://doi.org/10.1007/978-3-319-07911-0_12

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