Characterization and application of two RANK-specific antibodies with different biological activities.

Détails

Ressource 1Télécharger: 5_26773232_Postprint.pdf (1061.26 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_EFA8CC9CE127
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Characterization and application of two RANK-specific antibodies with different biological activities.
Périodique
Immunology Letters
Auteur(s)
Chypre M., Seaman J., Cordeiro O.G., Willen L., Knoop K.A., Buchanan A., Sainson R.C., Williams I.R., Yagita H., Schneider P., Mueller C.G.
ISSN
1879-0542 (Electronic)
ISSN-L
0165-2478
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
171
Pages
5-14
Langue
anglais
Résumé
Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-κB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-κB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools.
Mots-clé
Monoclonal antibody, RANK (TNFRSF11a), Langerhans cell, Epithelial microfold cell
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/04/2016 17:56
Dernière modification de la notice
20/08/2019 17:17
Données d'usage