Chapter

Fc Receptors

Volume 382 of the series Current Topics in Microbiology and Immunology pp 249-272

Date:

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

  • Dilip K. ChallaAffiliated withDepartment of Immunology, University of Texas Southwestern Medical Center
  • , Ramraj VelmuruganAffiliated withDepartment of Immunology, University of Texas Southwestern Medical Center
  • , Raimund J. OberAffiliated withDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Electrical Engineering, University of Texas at Dallas
  • , E. Sally WardAffiliated withDepartment of Immunology, University of Texas Southwestern Medical Center Email author 

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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.