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Title

Neutralization of macrophage migration inhibitory factor (MIF) by fully human antibodies correlates with their specificity for the beta-sheet structure of MIF

Authors
Kerschbaumer, Randolf J.
Rieger, Manfred
Volkel, Dirk
Le Roy, Didier
Roger, Thierry
Garbaraviciene, Jurate
Mullberg, Jurgen
show hidden authors show all authors [1 - 17]
Published in Journal of Biological Chemistry. 2012, vol. 287, no. 10, p. 7446-7455
Abstract The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that recently emerged as an attractive therapeutic target for a variety of diseases. A diverse panel of fully human anti-MIF antibodies was generated by selection from a phage display library and extensively analyzed in vitro. Epitope mapping studies identified antibodies specific for linear as well as structural epitopes. Experimental animal studies revealed that only those antibodies binding epitopes within amino acids 50-68 or 86-102 of the MIF molecule exerted protective effects in models of sepsis or contact hypersensitivity. Within the MIF protein, these two binding regions form a beta-sheet structure that includes the MIF oxidoreductase motif. We therefore conclude that this beta-sheet structure is a crucial region for MIF activity and a promising target for anti-MIF antibody therapy.
Keywords Amino Acid MotifsAnimalsAntibodies, Monoclonal/*chemistry/immunology/therapeutic useAntibodies, Neutralizing/*chemistry/immunology/therapeutic useDermatitis, Contact/drug therapy/immunologyDisease Models, AnimalHumansIntramolecular Oxidoreductases/*chemistry/immunologyMacrophage Migration-Inhibitory Factors/*chemistry/immunologyMiceSepsis/drug therapy/immunology
Identifiers
PMID: 22238348
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Other version: http://www.jbc.org/content/287/10/7446.full.pdf
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KERSCHBAUMER, Randolf J. et al. Neutralization of macrophage migration inhibitory factor (MIF) by fully human antibodies correlates with their specificity for the beta-sheet structure of MIF. In: Journal of Biological Chemistry, 2012, vol. 287, n° 10, p. 7446-7455. https://archive-ouverte.unige.ch/unige:29840

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Deposited on : 2013-09-20

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