Trogocytosis of chimeric antigen receptors between T cells is regulated by their transmembrane domains.

Abstract

Trogocytosis is an exchange of membrane-associated molecules between cells that can either halt or boost immune responses. However, the mechanism that regulates trogocytosis in T cells and its consequences are not yet clear. Here, we demonstrate that T cells can exchange chimeric antigen receptors (CARs) by trogocytosis, thereby arming recipient T cells with the capacity to respond to tumor antigens by up-regulating proteins associated with a cytotoxic response and killing of target cells. We demonstrate that although trogocytosis is dependent on cell-cell contact, the exchange of a specific cell membrane protein does not require a cognate binding partner on the surface of recipient cells. Instead, the probability that a protein is exchanged by trogocytosis is determined by its transmembrane domain. This finding opens new avenues for modulating this process in CAR-T cells.