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Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn

Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn
Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn

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.

Catabolism, IgG, Neonatal Fc receptor
0014-2980
2819-2825
Kim, Jin Kyoo
3f679975-b86c-4b96-9571-499c2ad80378
Firan, Mihail
4eb11e8f-7fb6-483b-99d2-3f918a4325c5
Radu, Caius G.
7b0cdea8-4ad8-4c89-89f7-eb6083504c1c
Kim, Cheol Hong
7a5648a8-2c26-4c43-8ecd-94c649187517
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Kim, Jin Kyoo
3f679975-b86c-4b96-9571-499c2ad80378
Firan, Mihail
4eb11e8f-7fb6-483b-99d2-3f918a4325c5
Radu, Caius G.
7b0cdea8-4ad8-4c89-89f7-eb6083504c1c
Kim, Cheol Hong
7a5648a8-2c26-4c43-8ecd-94c649187517
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Kim, Jin Kyoo, Firan, Mihail, Radu, Caius G., Kim, Cheol Hong, Ghetie, Victor and Ward, E. Sally (1999) Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn. European Journal of Immunology, 29 (9), 2819-2825. (doi:10.1002/(SICI)1521-4141(199909)29:09<2819::AID-IMMU2819>3.0.CO;2-6).

Record type: Article

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.

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More information

Published date: September 1999
Keywords: Catabolism, IgG, Neonatal Fc receptor

Identifiers

Local EPrints ID: 425130
URI: http://eprints.soton.ac.uk/id/eprint/425130
ISSN: 0014-2980
PURE UUID: c2de5a3b-aff0-4bff-bcfa-4e4d8af062c5
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 11 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Jin Kyoo Kim
Author: Mihail Firan
Author: Caius G. Radu
Author: Cheol Hong Kim
Author: Victor Ghetie
Author: E. Sally Ward ORCID iD

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