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Significance We have developed a method to screen for antibodies that can induce natural killer (NK) cell–mediated cytotoxicity. NK cells have the innate ability to identify and kill target cells. Antibodies that bind to NK cell surface proteins are anchored to the cell surface of a target cell line and probed for their abilities to stimulate NK cytotoxicity. Target cells displaying antibodies that induce NK cell–mediated cytotoxicity are depleted from the antibody pool. Because the antibodies are based on the same scaffold, antibodies on surviving target cells can be identified through next generation sequencing of complementarity determining region H3. This method facilitates the identification of antibodies that can stimulate immune cell activation and may be used to desig immunotherapies.

A functional mammalian display screen identifies rare antibodies that stimulate NK cell–mediated cytotoxicity