Trogocytosis of chimeric antigen receptors between T cells is regulated by their transmembrane domains
Stefano Barbera, Matthijs J. A. Schuiling, Nathaniel A. Sanjaya, Ilkka Pietilä, Tina Sarén, Magnus Essand, Anna Dimberg
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.