Human single-chain variable fragment antibody inhibits macrophage migration inhibitory factor tautomerase activity

Tarasuk,Mayuri; Poungpair,Ornnuthchar; Ungsupravate,Duangporn; Bangphoomi,Kunan; Chaicumpa,Wanpen; Yenchitsomanus,Pa-Thai

doi:10.3892/ijmm.2014.1622

Human single-chain variable fragment antibody inhibits macrophage migration inhibitory factor tautomerase activity

Authors:
- Mayuri Tarasuk
- Ornnuthchar Poungpair
- Duangporn Ungsupravate
- Kunan Bangphoomi
- Wanpen Chaicumpa
- Pa-Thai Yenchitsomanus
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Affiliations: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Department of Biochemistry, Faculty of Sciences, Kasetsart University, Bangkok, Thailand, Laboratory for Research and Technology Development, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Published online on: January 13, 2014 https://doi.org/10.3892/ijmm.2014.1622
Pages: 515-522
Copyright: © Tarasuk et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, secreted from a variety of immune cells, that regulates innate and adaptive immune responses. Elevation of MIF levels in plasma correlates with the severity of inflammatory diseases in humans. Inhibition of MIF or its tautomerase activity ameliorates disease severity by reducing inflammatory responses. In this study, the human single-chain variable fragment (HuScFv) antibody specific to MIF was selected from the human antibody phage display library by using purified recombinant full-length human MIF (rMIF) as the target antigen. Monoclonal HuScFv was produced from phage-transformed bacteria and tested for their binding activities to rMIF by indirect enzyme-linked immunosorbent assay as well as to native MIF by western blot analysis and immunofluorescence assay. The HuScFv with highest binding signal to rMIF also inhibited the tautomerase activities of both rMIF and native MIF in human monoblastic leukemia (U937) cells in a dose-dependent manner. Mimotope searching and molecular docking concordantly demonstrated that the HuScFv interacted with Lys32 and Ile64 in the MIF tautomerase active site. To the best of our knowledge, this is the first study to focus on MIF-specific fully-human antibody fragment with a tautomerase-inhibitory effect that has potential to be developed as anti-inflammatory biomolecules for human use.

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