Trogocytosis of CARs depends on transmembrane domains

Abstract

Immune cells can exchange membrane-bound molecules via horizontal protein transfer, a poorly understood process termed trogocytosis. Barbera et al. now show that chimeric antigen receptor (CAR)-engineered T cells can transfer their CARs to T cells and other cells by trogocytosis in vivo. CARs on recipient T cells seemed to be functional, as isolated recipient cells were able to kill target cells. Trogocytosis did not depend on a cognate binding partner for the transferred protein, as had been proposed previously. Instead, the probability of a horizontal CAR transfer was determined by its transmembrane domain and its likelihood to localize to the tips of microvilli. These findings have important implications for CAR design.