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

Kerschbaumer, Randolf J.; Rieger, Manfred; Volkel, Dirk; Le Roy, Didier; Roger, Thierry; Garbaraviciene, Jurate; Boehncke, Wolf-Henning; Mullberg, Jurgen; Hoet, Rene M.; Wood, Clive R.; Antoine, Gerhard; Thiele, Michael; Savidis-Dacho, Helga; Dockal, Michael; Ehrlich, Hartmut; Calandra, Thierry; Scheiflinger, Friedrich

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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 Boehncke, Wolf-Henning Mullberg, Jurgen Hoet, Rene M. Wood, Clive R. Antoine, Gerhard Thiele, Michael Savidis-Dacho, Helga Dockal, Michael Ehrlich, Hartmut Calandra, Thierry Scheiflinger, Friedrich 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 Motifs — Animals — Antibodies, Monoclonal/chemistry/immunology/therapeutic use — Antibodies, Neutralizing/chemistry/immunology/therapeutic use — Dermatitis, Contact/drug therapy/immunology — Disease Models, Animal — Humans — Intramolecular Oxidoreductases/chemistry/immunology — Macrophage Migration-Inhibitory Factors/chemistry/immunology — Mice — Sepsis/drug therapy/immunology
Identifiers		DOI: 10.1074/jbc.M111.329664 PMID: 22238348
Full text		Article - Limited access to UNIGE Other version: http://www.jbc.org/content/287/10/7446.full.pdf
Citation (ISO format)		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