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The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of γ-globulin in humans

The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of γ-globulin in humans
The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of γ-globulin in humans

The transfer of maternal γ-globulin (IgG) provides the neonate with humoral immunity during early life. In humans, maternal IgG is transported across the placenta during the third trimester of pregnancy. The expression of the MHC class I-related receptor, FcRn, in the human placenta suggests that this Fc receptor might be involved in the delivery of maternal IgG, but direct evidence to support this is lacking. In the current study an ex vivo placental model has been used to analyze the maternofetal transfer of a recombinant, humanized (IgG1) antibody in which His435 has been mutated to alanine (H435A). In vitro binding studies using surface plasmon resonance indicate that the mutation ablates binding of the antibody to recombinant mouse and human FcRn. Relative to the wild-type antibody, the H435A mutant is deficient in transfer across the placenta. Significantly, the mutation does not affect binding to FcγRIII, an FcR that has been suggested in earlier studies to mediate the transfer of maternal IgG. The analyses demonstrate that binding of an IgG to FcRn is a prerequisite for transport across the perfused placenta. FcRn therefore plays a central role in the maternofetal delivery of IgG and this has implications for the use of protein engineering to improve the properties of therapeutic antibodies.

Catabolism, Human IgG, Neonatal Fc receptor, Placental transport
0953-8178
993-1002
Firan, Mihail
4eb11e8f-7fb6-483b-99d2-3f918a4325c5
Bawdon, Roger
c7a99f9d-00f9-4d82-8593-e41641819956
Radu, Caius
cf50ccf6-c03c-4d8f-abd8-56681251f990
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Eaken, Darla
ee2a5e96-8d42-45a4-a11b-12128607bd3b
Antohe, Felicia
7723c6d9-3905-4016-a6ff-b18ac5d575f9
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Firan, Mihail
4eb11e8f-7fb6-483b-99d2-3f918a4325c5
Bawdon, Roger
c7a99f9d-00f9-4d82-8593-e41641819956
Radu, Caius
cf50ccf6-c03c-4d8f-abd8-56681251f990
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Eaken, Darla
ee2a5e96-8d42-45a4-a11b-12128607bd3b
Antohe, Felicia
7723c6d9-3905-4016-a6ff-b18ac5d575f9
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Firan, Mihail, Bawdon, Roger, Radu, Caius, Ober, Raimund J., Eaken, Darla, Antohe, Felicia, Ghetie, Victor and Ward, E. Sally (2001) The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of γ-globulin in humans. International Immunology, 13 (8), 993-1002. (doi:10.1093/intimm/13.8.993).

Record type: Article

Abstract

The transfer of maternal γ-globulin (IgG) provides the neonate with humoral immunity during early life. In humans, maternal IgG is transported across the placenta during the third trimester of pregnancy. The expression of the MHC class I-related receptor, FcRn, in the human placenta suggests that this Fc receptor might be involved in the delivery of maternal IgG, but direct evidence to support this is lacking. In the current study an ex vivo placental model has been used to analyze the maternofetal transfer of a recombinant, humanized (IgG1) antibody in which His435 has been mutated to alanine (H435A). In vitro binding studies using surface plasmon resonance indicate that the mutation ablates binding of the antibody to recombinant mouse and human FcRn. Relative to the wild-type antibody, the H435A mutant is deficient in transfer across the placenta. Significantly, the mutation does not affect binding to FcγRIII, an FcR that has been suggested in earlier studies to mediate the transfer of maternal IgG. The analyses demonstrate that binding of an IgG to FcRn is a prerequisite for transport across the perfused placenta. FcRn therefore plays a central role in the maternofetal delivery of IgG and this has implications for the use of protein engineering to improve the properties of therapeutic antibodies.

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More information

Accepted/In Press date: 26 April 2001
Published date: 1 August 2001
Keywords: Catabolism, Human IgG, Neonatal Fc receptor, Placental transport

Identifiers

Local EPrints ID: 424920
URI: http://eprints.soton.ac.uk/id/eprint/424920
ISSN: 0953-8178
PURE UUID: 96a2bb79-ba63-4bf4-9af4-9ec791ea4482
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 05 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Mihail Firan
Author: Roger Bawdon
Author: Caius Radu
Author: Raimund J. Ober ORCID iD
Author: Darla Eaken
Author: Felicia Antohe
Author: Victor Ghetie
Author: E. Sally Ward ORCID iD

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