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The stoichiometry and affinity of the interaction of murine Fc fragments with the MHC class I-related receptor, FcRn

The stoichiometry and affinity of the interaction of murine Fc fragments with the MHC class I-related receptor, FcRn
The stoichiometry and affinity of the interaction of murine Fc fragments with the MHC class I-related receptor, FcRn

The binding of recombinant wild type and mutant Fc-hinge fragments to soluble, FcRn expressed in insect cells has been analysed. The mutant Fc-hinge fragments are derived from murine IgG1 with mutation of residues located at the CH2-CH3 domain interface (Ile253, His310, Gln311, His433 and Asn434; EU numbering). These mutant Fc-hinge fragments have previously been shown to be deficient in neonatal transcytosis in suckling mice and also have abnormally short serum half lives. The mutated residues are highly conserved in human and rodent gammaglobulins (IgGs) and are also involved in binding to staphylococcal protein A. This study demonstrates that the Fc mutants have lower binding affinities for recombinant FcRn and mutations in the CH2 domain have a greater effect than those in the CH3 domain. There is an excellent correlation between affinity and transcytosis or the control of catabolism, and this provides further evidence in support of the close overlap of the sites of IgG/Fc involved in these processes. The stoichiometry of the FcRn:Fc interaction has also been investigated and has been found to be 1:1, indicating that binding of FcRn to one CH2-CH3 domain interface site precludes an FcRn:Fc interaction at the second site.

Affinity, Fc receptor, Recombinant Fc fragment, Stoichiometry, Transcytosis
0161-5890
521-530
Popov, Sergei
15a37b99-253a-43a4-b825-19cd4e9b150e
Hubbard, James G.
8394863f-e859-4e83-8d13-7f19e5760264
Kim, Jin Kyoo
3f679975-b86c-4b96-9571-499c2ad80378
Ober, Bertram
fdc0003e-6a7a-4894-bd4a-32d9d27f7c93
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Popov, Sergei
15a37b99-253a-43a4-b825-19cd4e9b150e
Hubbard, James G.
8394863f-e859-4e83-8d13-7f19e5760264
Kim, Jin Kyoo
3f679975-b86c-4b96-9571-499c2ad80378
Ober, Bertram
fdc0003e-6a7a-4894-bd4a-32d9d27f7c93
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Popov, Sergei, Hubbard, James G., Kim, Jin Kyoo, Ober, Bertram, Ghetie, Victor and Ward, E. Sally (1996) The stoichiometry and affinity of the interaction of murine Fc fragments with the MHC class I-related receptor, FcRn. Molecular Immunology, 33 (6), 521-530. (doi:10.1016/0161-5890(96)00004-1).

Record type: Article

Abstract

The binding of recombinant wild type and mutant Fc-hinge fragments to soluble, FcRn expressed in insect cells has been analysed. The mutant Fc-hinge fragments are derived from murine IgG1 with mutation of residues located at the CH2-CH3 domain interface (Ile253, His310, Gln311, His433 and Asn434; EU numbering). These mutant Fc-hinge fragments have previously been shown to be deficient in neonatal transcytosis in suckling mice and also have abnormally short serum half lives. The mutated residues are highly conserved in human and rodent gammaglobulins (IgGs) and are also involved in binding to staphylococcal protein A. This study demonstrates that the Fc mutants have lower binding affinities for recombinant FcRn and mutations in the CH2 domain have a greater effect than those in the CH3 domain. There is an excellent correlation between affinity and transcytosis or the control of catabolism, and this provides further evidence in support of the close overlap of the sites of IgG/Fc involved in these processes. The stoichiometry of the FcRn:Fc interaction has also been investigated and has been found to be 1:1, indicating that binding of FcRn to one CH2-CH3 domain interface site precludes an FcRn:Fc interaction at the second site.

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More information

Accepted/In Press date: 19 December 1995
Published date: April 1996
Keywords: Affinity, Fc receptor, Recombinant Fc fragment, Stoichiometry, Transcytosis

Identifiers

Local EPrints ID: 425116
URI: https://eprints.soton.ac.uk/id/eprint/425116
ISSN: 0161-5890
PURE UUID: a123e1e7-b785-4de8-9f05-1ddb001ff63b
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: 05 Nov 2019 01:23

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Contributors

Author: Sergei Popov
Author: James G. Hubbard
Author: Jin Kyoo Kim
Author: Bertram Ober
Author: Victor Ghetie
Author: E. Sally Ward ORCID iD

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