title: Neutralization of macrophage migration inhibitory factor (MIF) by fully human antibodies correlates with their specificity for the β-sheet structure of MIF.
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 β-sheet structure that includes the MIF oxidoreductase motif. We therefore conclude that this β-sheet structure is a crucial region for MIF activity and a promising target for anti-MIF antibody therapy.
authors.affiliation: Baxter Biomedical Research Center, Baxter Innovations GmbH, A-2304 Orth/Donau, Austria. randolf_kerschbaumer@baxter.com
authors.forename: Randolf J
authors.initials: RJ
authors.lastname: Kerschbaumer
authors.forename: Manfred
authors.initials: M
authors.lastname: Rieger
authors.forename: Dirk
authors.initials: D
authors.lastname: Völkel
authors.forename: Didier
authors.initials: D
authors.lastname: Le Roy
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Jurate
authors.initials: J
authors.lastname: Garbaraviciene
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müllberg
authors.forename: Rene M
authors.initials: RM
authors.lastname: Hoet
authors.forename: Clive R
authors.initials: CR
authors.lastname: Wood
authors.forename: Gerhard
authors.initials: G
authors.lastname: Antoine
authors.forename: Michael
authors.initials: M
authors.lastname: Thiele
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Michael
authors.initials: M
authors.lastname: Dockal
authors.forename: Hartmut
authors.initials: H
authors.lastname: Ehrlich
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000737:chemistry* / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C076231:Mif protein, mouse