title: Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn.
abstract: The analysis of the pharmacokinetics of wild-type and mutated Fc fragments derived from human IgG1 indicates that Ile253, His310 and His435 play a central role in regulating serum half-life in mice. Reduced serum half-life of the recombinant, mutated fragments correlates with decreased binding to the MHC class I-related neonatal Fc receptor, FcRn. In addition, the analysis of an Fc fragment in which His435 is mutated to Arg435 demonstrates that the sequence difference at this position between human IgG1 (His435) and IgG3 (Arg435) most likely accounts for the shorter serum half-life of IgG3 relative to IgG1. In contrast to His310 and His435, the data indicate that His433 does not play a role in regulating the serum half-life of human IgG1. Thus, the interaction site of mouse FcRn on human and mouse IgG1 involves the same conserved amino acids located at the CH2-CH3 domain interface of the IgG molecule. The sequence similarities between mouse and human FcRn suggest that these studies have direct relevance to understanding the factors that govern the pharmacokinetics of therapeutic IgG.
authors.affiliation: Department of Microbiology, Changwon National University, Changwon, Kyungnam, South Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Firan
authors.forename: C G
authors.initials: CG
authors.lastname: Radu
authors.forename: C H
authors.initials: CH
authors.lastname: Kim
authors.forename: V
authors.initials: V
authors.lastname: Ghetie
authors.forename: E S
authors.initials: ES
authors.lastname: Ward
mesh_terms: D000818:Animals; D018604:Epitope Mapping / Q000379:methods*; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal