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dc.contributor.authorSubías Hidalgo, Marta
dc.contributor.authorYébenes, Hugo
dc.contributor.authorRodríguez-Gallego, César
dc.contributor.authorMartín-Ambrosio, Adrián
dc.contributor.authorDominguez-Rodriguez, Mercedes 
dc.contributor.authorTortajada, Agustin
dc.contributor.authorRodríguez de Córdoba, Santiago
dc.contributor.authorLlorca Blanco, Oscar Antonio 
dc.date.accessioned2019-02-12T14:44:03Z
dc.date.available2019-02-12T14:44:03Z
dc.date.issued2017
dc.identifier.citationEur J Immunol. 2017 Mar;47(3):504-515.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7168
dc.description.abstractC3 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.es_ES
dc.description.sponsorshipWork 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.es_ES
dc.language.isoenges_ES
dc.publisherWiley es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectC3es_ES
dc.subjectC3bes_ES
dc.subjectC3bBb convertasees_ES
dc.subjectComplement inhibitiones_ES
dc.subjectMonoclonal antibodyes_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntibodies, Monoclonal es_ES
dc.subject.meshAntigen-Antibody Complex es_ES
dc.subject.meshComplement C3 es_ES
dc.subject.meshComplement C3-C5 Convertases es_ES
dc.subject.meshGenetic Engineering es_ES
dc.subject.meshHemolytic Plaque Technique es_ES
dc.subject.meshHumans es_ES
dc.subject.meshHybridomas es_ES
dc.subject.meshImmunoglobulin Fab Fragments es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshProtein Conformation es_ES
dc.subject.meshComplement Pathway, Alternativees_ES
dc.titleFunctional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applicationses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-SinObraDerivadas 4.0 Internacional*
dc.identifier.pubmedID28083930es_ES
dc.format.volume47es_ES
dc.format.number3es_ES
dc.format.page504-515es_ES
dc.identifier.doi10.1002/eji.201646758es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderUnión Europea. Comisión Europea. 7 Programa Marco 
dc.contributor.funderComunidad de Madrid (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1521-4141es_ES
dc.relation.publisherversionhttps://doi.org/10.1002/eji.201646758es_ES
dc.identifier.journalEuropean journal of immunologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/305608es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011‐26583es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015‐66287‐Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014‐52301‐Res_ES
dc.rights.accessRightsopen accesses_ES


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Atribución-NoComercial-SinObraDerivadas 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-SinObraDerivadas 4.0 Internacional