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FcRn: From molecular interactions to regulation of IgG pharmacokinetics and functions

FcRn: From molecular interactions to regulation of IgG pharmacokinetics and functions
FcRn: From molecular interactions to regulation of IgG pharmacokinetics and functions

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.

0070-217X
249-272
Springer
Challa, Dilip K.
433af413-17a0-4c55-b86f-21e4e5cedd6f
Velmurugan, Ramraj
4f2d41cd-90eb-4f61-b5e0-df6308726d28
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Daeron, M.
Nimmerjahn, F.
Challa, Dilip K.
433af413-17a0-4c55-b86f-21e4e5cedd6f
Velmurugan, Ramraj
4f2d41cd-90eb-4f61-b5e0-df6308726d28
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Daeron, M.
Nimmerjahn, F.

Challa, Dilip K., Velmurugan, Ramraj, Ober, Raimund J. and Ward, E. Sally (2014) FcRn: From molecular interactions to regulation of IgG pharmacokinetics and functions. In, Daeron, M. and Nimmerjahn, F. (eds.) Fc Receptors. (Current Topics in Microbiology and Immunology, 382) Springer, pp. 249-272. (doi:10.1007/978-3-319-07911-0_12).

Record type: Book Section

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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More information

e-pub ahead of print date: 12 August 2014
Published date: 2014

Identifiers

Local EPrints ID: 423657
URI: http://eprints.soton.ac.uk/id/eprint/423657
ISSN: 0070-217X
PURE UUID: dadadabb-36dd-4d2d-9b9a-4c7fd2332fd2
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 27 Sep 2018 16:30
Last modified: 16 Mar 2024 04:37

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Contributors

Author: Dilip K. Challa
Author: Ramraj Velmurugan
Author: Raimund J. Ober ORCID iD
Author: E. Sally Ward ORCID iD
Editor: M. Daeron
Editor: F. Nimmerjahn

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