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mAbs Volume 3, 2011 - Issue 5
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Review

Neonatal Fc receptor and IgG-based therapeutics

Timothy T. Kuo Division of Gastroenterology, Department of Medicine, Brigham & Women’s Hospital, Harvard Medical School; Boston, MA USACorrespondence[email protected]
&
Victoria G. Aveson Division of Gastroenterology, Department of Medicine, Brigham & Women’s Hospital, Harvard Medical School; Boston, MA USA
Pages 422-430 | Received 14 Jun 2011, Accepted 23 Jul 2011, Published online: 01 Sep 2011

Figures & data

Figure 1 FcRn mediates bidirectional transport and membrane recycling of IgG in epithelial cells. IgG is believed to enter the cell by fluid phase pintocytosis (assuming neutral pH condition) and does not bind to FcRn until the endosome is acidified. However, in the duodenum, the acidic luminal environment may allow IgG to bind to FcRn at the apical membrane surface before endocytosis.Citation79 Two FcRn bind to a single IgG molecule. IgG may be transcytosed to the opposite membrane surface or recycled back to the same membrane surface.Citation11 The exact intracellular pathway is believed to differ between cells. IgG is dissociated from FcRn at the membrane surface at neutral pH.

Figure 1 FcRn mediates bidirectional transport and membrane recycling of IgG in epithelial cells. IgG is believed to enter the cell by fluid phase pintocytosis (assuming neutral pH condition) and does not bind to FcRn until the endosome is acidified. However, in the duodenum, the acidic luminal environment may allow IgG to bind to FcRn at the apical membrane surface before endocytosis.Citation79 Two FcRn bind to a single IgG molecule. IgG may be transcytosed to the opposite membrane surface or recycled back to the same membrane surface.Citation11 The exact intracellular pathway is believed to differ between cells. IgG is dissociated from FcRn at the membrane surface at neutral pH.

Figure 2 Mutations in amino acid residues in the Fc region to enhance FcRn affinity. Diagram of the Fc portion of human IgG1 (protein data bank (PDB) ID: 1DN2) was generated using RasMol (OpenRasMol).Citation80 FcRn binds at the CH2–CH3 hinge region of Fc at I253, H310, H430, and to a lesser extent H433 and Y436.Citation12–Citation14 Amino acid residues near the Fc hinge region mutated to increase binding to FcRn are grouped in colors according to the various combination listed in .

Figure 2 Mutations in amino acid residues in the Fc region to enhance FcRn affinity. Diagram of the Fc portion of human IgG1 (protein data bank (PDB) ID: 1DN2) was generated using RasMol (OpenRasMol).Citation80 FcRn binds at the CH2–CH3 hinge region of Fc at I253, H310, H430, and to a lesser extent H433 and Y436.Citation12–Citation14 Amino acid residues near the Fc hinge region mutated to increase binding to FcRn are grouped in colors according to the various combination listed in Table 1.

Table 1 A summary of IgG mutations developed to increase FcRn-IgG binding affinity and extend serum half-life

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