Neutralization of Macrophage Migration Inhibitory Factor (MIF) by Fully Human Antibodies Correlates with Their Specificity for the β-Sheet Structure of MIF.


Autoria(s): Kerschbaumer R.J.; Rieger M.; Völkel D.; Le Roy D.; Roger T.; Garbaraviciene J.; Boehncke W.H.; Müllberg J.; Hoet R.M.; Wood C.R.; Antoine G.; Thiele M.; Savidis-Dacho H.; Dockal M.; Ehrlich H.; Calandra T.; Scheiflinger F.
Data(s)

2012

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_73FC2C8192D5

isbn:1083-351X (Electronic)

pmid:22238348

doi:10.1074/jbc.M111.329664

isiid:000301060200045

Idioma(s)

en

Fonte

Journal of Biological Chemistry, vol. 287, no. 10, pp. 7446-7455

Tipo

info:eu-repo/semantics/article

article