2026-06-14T03:33:35Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71682025-05-07T10:54:37Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Subías Hidalgo, Marta
author
Yébenes, Hugo
author
Rodríguez-Gallego, César
author
Martín-Ambrosio, Adrián
author
Dominguez-Rodriguez, Mercedes
author
Tortajada, Agustin
author
Rodriguez de Cordoba, Santiago
author
Llorca Blanco, Oscar Antonio
funder
Comunidad de Madrid (España)
funder
Unión Europea. Comisión Europea. 7 Programa Marco
funder
Ministerio de Economía y Competitividad (España)
2019-02-12T14:44:03Z
2019-02-12T14:44:03Z
2017
Eur J Immunol. 2017 Mar;47(3):504-515.
10.1002/eji.201646758
1521-4141
European journal of immunology
28083930
http://hdl.handle.net/20.500.12105/7168
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.
eng
C3
C3b
C3bBb convertase
Complement inhibition
Monoclonal antibody
Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications
research article
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FunctionalAndStructuralCharacterization_2017.pdf.txt