Abstract
Despite the increasing importance of rabbit as an animal model in pharmacological studies like investigating placental transfer of therapeutic IgGs, little is known about the molecular interaction of the rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG molecules. We analyzed the interactions of the rabbit and human FcRn with rabbit and human IgG isotypes using surface plasmon resonance assay. Similar to FcRn of other species, rabbit FcRn functions in pH-dependent manner, as it binds IgGs at pH 6.0, but no binding occurs at pH 7.4. We also showed that rabbit FcRn binds rabbit IgG and human IgG1 with nearly identical affinity, whereas it has stronger interactions with the other human IgG isotypes. The similar affinity of rabbit IgG and human IgG1 for rabbit FcRn was confirmed by in vitro FcRn-mediated recycling assay. These data verify that rabbit is an appropriate animal model for analyzing the pharmacokinetics of human therapeutic monoclonal antibodies.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Chromatography, Gel
-
Histocompatibility Antigens Class I / chemistry
-
Histocompatibility Antigens Class I / metabolism*
-
Humans
-
Immunoglobulin G / chemistry
-
Immunoglobulin G / metabolism*
-
Macrophages / metabolism
-
Rabbits
-
Receptors, Fc / chemistry
-
Receptors, Fc / metabolism*
-
Sequence Homology, Amino Acid
-
Surface Plasmon Resonance
Substances
-
Histocompatibility Antigens Class I
-
Immunoglobulin G
-
Receptors, Fc
-
Fc receptor, neonatal
Grants and funding
This work was supported by the grant from the Hungarian National Development Agency [KMOP-4.2.1./B-10-2011-0002]. The funder provided support in the form of purchasing the ProteOn XPR36 biosensor instrument, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. BB is scientific researcher, IK is CEO of ImmunoGenes-ABS Ltd, Budakeszi, Hungary. The funder provided support in the form of salaries for authors BB and IK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.