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Generation of a highly diverse panel of antagonistic chicken monoclonal antibodies against the GIP receptor.

mAbs (2017-01-06)
Jennifer D Könitzer, Shreya Pramanick, Qi Pan, Robert Augustin, Sebastian Bandholtz, William Harriman, Shelley Izquierdo
ABSTRACT

Raising functional antibodies against G protein-coupled receptors (GPCRs) is challenging due to their low density expression, instability in the absence of the cell membrane's lipid bilayer and frequently short extracellular domains that can serve as antigens. In addition, a particular therapeutic concept may require an antibody to not just bind the receptor, but also act as a functional receptor agonist or antagonist. Antagonizing the glucose-dependent insulinotropic polypeptide (GIP) receptor may open up new therapeutic modalities in the treatment of diabetes and obesity. As such, a panel of monoclonal antagonistic antibodies would be a useful tool for in vitro and in vivo proof of concept studies. The receptor is highly conserved between rodents and humans, which has contributed to previous mouse and rat immunization campaigns generating very few usable antibodies. Switching the immunization host to chicken, which is phylogenetically distant from mammals, enabled the generation of a large and diverse panel of monoclonal antibodies containing 172 unique sequences. Three-quarters of all chicken-derived antibodies were functional antagonists, exhibited high-affinities to the receptor extracellular domain and sampled a broad epitope repertoire. For difficult targets, including GPCRs such as GIPR, chickens are emerging as valuable immunization hosts for therapeutic antibody discovery.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
N-羟基硫代琥珀酰亚胺 钠盐, ≥98% (HPLC)
Sigma-Aldrich
抗-鸡 IgY(IgG)(全分子)−过氧化物酶 兔抗, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Gastric Inhibitory Polypeptide human, ≥95% (HPLC)