Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications

41 p.-11 fig.

Detalles Bibliográficos
Autores: Subías, Marta, Yébenes, Hugo, Rodríguez-Gallego, César, Martín-Ambrosio, Adrián, Domínguez, Mercedes, Tortajada, Agustín, Rodríguez de Córdoba, Santiago, Llorca, Óscar
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/149504
Acceso en línea:http://hdl.handle.net/10261/149504
Access Level:acceso abierto
Palabra clave:Complement inhibition
Monoclonal antibody
C3
C3b
C3bBb convertase
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spelling Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applicationsSubías, MartaYébenes, HugoRodríguez-Gallego, CésarMartín-Ambrosio, AdriánDomínguez, MercedesTortajada, AgustínRodríguez de Córdoba, SantiagoLlorca, ÓscarComplement inhibitionMonoclonal antibodyC3C3bC3bBb convertase41 p.-11 fig.C3 is the central component of the complement system. Upon activation, C3 sequentially generates various proteolytic fragments, C3a, C3b, iC3b, C3dg, each of them exposing novel surfaces, which are sites of interaction with other proteins. C3 and its fragments are therapeutic targets and markers of complement activation. We report the structural and functional characterization of four monoclonal antibodies (mAbs) generated by immunizing C3-deficient mice with a mixture of human C3b, iC3b and C3dg fragments, and discuss their potential applications. This collection includes three mAbs interacting with native C3 and inhibiting AP complement activation; two of them by blocking the cleavage of C3 by the AP C3-converase and one by impeding formation of the AP C3-convertase. The interaction sites of these mAbs in the target molecules were determined by resolving the structures of Fab fragments bound to C3b and/or iC3b using electron microscopy. A fourth mAb specifically recognizes the iC3b, C3dg, and C3d fragments. It binds to an evolutionary-conserved neoepitope generated after C3b cleavage by FI, detecting iC3b/C3dg deposition over opsonized surfaces by flow cytometry and immunohistochemistry in human and other species. Because well-characterized anti-complement mAbs are uncommon, the mAbs reported here may offer interesting therapeutic and diagnostic opportunities.Work in this report has been funded by the Spanish “Ministerio de Economía y Competitividad” (SAF2011-26583 and SAF2015-66287-R to SRdC and SAF2014- 52301-R to OL) and the Seventh Framework Programme European Union Project EURenOmics (305608) to SRdC. In addition, this work has been supported by a grant from the Autonomous Region of Madrid (S2010/BMD-2316) to SRdeC and OL.Peer reviewedWiley-VCHMinisterio de Economía y Competitividad (España)European CommissionComunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201720172017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/149504reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/305608http://dx.doi.org/10.1002/eji.201646758Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1495042026-05-22T06:33:51Z
dc.title.none.fl_str_mv Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
title Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
spellingShingle Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
Subías, Marta
Complement inhibition
Monoclonal antibody
C3
C3b
C3bBb convertase
title_short Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
title_full Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
title_fullStr Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
title_full_unstemmed Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
title_sort Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
dc.creator.none.fl_str_mv Subías, Marta
Yébenes, Hugo
Rodríguez-Gallego, César
Martín-Ambrosio, Adrián
Domínguez, Mercedes
Tortajada, Agustín
Rodríguez de Córdoba, Santiago
Llorca, Óscar
author Subías, Marta
author_facet Subías, Marta
Yébenes, Hugo
Rodríguez-Gallego, César
Martín-Ambrosio, Adrián
Domínguez, Mercedes
Tortajada, Agustín
Rodríguez de Córdoba, Santiago
Llorca, Óscar
author_role author
author2 Yébenes, Hugo
Rodríguez-Gallego, César
Martín-Ambrosio, Adrián
Domínguez, Mercedes
Tortajada, Agustín
Rodríguez de Córdoba, Santiago
Llorca, Óscar
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Complement inhibition
Monoclonal antibody
C3
C3b
C3bBb convertase
topic Complement inhibition
Monoclonal antibody
C3
C3b
C3bBb convertase
description 41 p.-11 fig.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/149504
url http://hdl.handle.net/10261/149504
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/305608
http://dx.doi.org/10.1002/eji.201646758
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-VCH
publisher.none.fl_str_mv Wiley-VCH
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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