Barbera Stefano, Schuiling Matthijs J A, Sanjaya Nathaniel A, Pietilä Ilkka, Sarén Tina, Essand Magnus, Dimberg Anna
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Sci Immunol. 2025 Jan 31;10(103):eado2054. doi: 10.1126/sciimmunol.ado2054.
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.
噬细胞作用是细胞间膜相关分子的交换，这一过程既能终止也能增强免疫反应。然而，调节T细胞中噬细胞作用的机制及其后果尚不清楚。在此，我们证明T细胞可通过噬细胞作用交换嵌合抗原受体（CAR），从而使受体T细胞具备通过上调与细胞毒性反应及杀伤靶细胞相关的蛋白质来响应肿瘤抗原的能力。我们证明，尽管噬细胞作用依赖于细胞间接触，但特定细胞膜蛋白的交换并不需要受体细胞表面的同源结合伴侣。相反，一种蛋白质通过噬细胞作用进行交换的概率由其跨膜结构域决定。这一发现为调控CAR-T细胞中的这一过程开辟了新途径。
