A cell–cell interaction format for selection of high-affinity antibodies to membrane proteins

Significance Antibodies are an important class of drugs. We developed a simple, easy-to-use method for antibody drug discovery targeting membrane proteins including gated ion channels and G protein-coupled receptors. While phage or yeast display provides a convenient tool for antibody screening, the development of therapeutic antibodies against membrane proteins still encounters bottlenecks, because it is usually difficult to purify membrane proteins in native conformation for selecting functional antibodies. To address this challenge, we designed a whole-cell screening platform based on yeast–mammalian cell interaction, which bypasses the step of membrane protein purification and enables the direct selection of antibodies against “difficult-to-purify membrane proteins” in native state.