Selectivity of anti-GPCR antibodies


In a recent publication in Science Advances, the selectivity of antibodies against subfamilies of G protein-coupled receptors (GPCRs) was investigated using a multiplexed immunoassay and a customized library of solubilized GPCRs.

GPCRs are essential mediators of extracellular signals and interesting targets for developing therapeutic agents, such as anti-GPCR antibodies. However, the nature and sequence similarities between individual membrane receptors can pose a challenge to finding the selective and most suitable antibodies for the intended application. This study developed a multiplexed immunoassay to test more than 400 anti-GPCR antibodies produced by the Human Protein Atlas against more than 200 engineered GPCR proteins. The results showed that the majority of the antibodies bound selectively to their intended and solubilized GPCR target, with a smaller fraction showing off-target or non-target binding. Besides experimental selectivity assessment, the authors also used structural prediction to investigate common features of the antigens from on-target antibodies and why these differed for those related to off-target binding. The study involved research groups from Science for Life Laboratory (SciLifeLab), Stockholm, Sweden and The Rockefeller University, NY, USA.

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