Trogocytosis is a biological process involving the rapid, direct transfer of membrane components between two living cells. This form of communication allows one cell to physically extract and ingest small “bites” of material from the surface of another cell. This highly dynamic mechanism of intercellular exchange results in the swift acquisition of functional proteins and lipids by the recipient cell. Trogocytosis serves as a powerful method for cells to modify their own surface properties and influence the function of their neighbors.
Defining the Membrane Transfer Process
Trogocytosis is fundamentally distinct from phagocytosis, which is a process where a cell completely engulfs and usually destroys another cell or a large particle. Unlike this more aggressive “devouring,” trogocytosis involves only the removal of small, non-lethal patches of the plasma membrane, receptors, and sometimes associated cytosolic components. The process requires intimate, direct contact between the two living cells, making it a contact-dependent form of communication.
This interaction is initiated by receptor-ligand binding, often resulting in the formation of a transient cellular junction known as an immunological synapse, particularly among immune cells. The recipient cell actively pulls a fragment of the donor cell’s membrane. Specifically, the process is dependent on the actin cytoskeleton and signaling molecules like Phosphoinositide 3-kinase (PI3K) and various small GTPases, which drive the membrane bending and scission necessary for the transfer.
The rapid kinetics of trogocytosis are a defining feature, often occurring within minutes of cell-to-cell contact, which is much faster than other modes of intercellular exchange like cell fusion. The transferred membrane fragment, complete with intact proteins, is then integrated into the recipient cell’s own surface. This transfer results in a gain of function for the recipient cell and a corresponding loss of function for the donor cell, without necessarily leading to the donor cell’s immediate death.
Cell Types Involved in Trogocytosis
Trogocytosis is most extensively studied in the immune system. The primary immune cells known to engage in this process include T cells, B cells, and Natural Killer (NK) cells. These lymphocytes actively extract membrane fragments from antigen-presenting cells (APCs) during their interactions.
Other immune cells, such as macrophages and neutrophils, also exhibit trogocytic behavior. They often utilize this mechanism to interact with target cells, sometimes leading to cell killing or the removal of therapeutic antibodies. Beyond the mammalian immune system, the process is evolutionarily conserved and found in non-immune cells and even parasitic organisms. Notably, the intestinal parasite Entamoeba histolytica performs trogocytosis to “nibble” live human cells.
Roles in Immune Cell Communication
Trogocytosis plays a sophisticated role in fine-tuning the immune response. One of the most significant functions is in antigen presentation, where immune cells acquire Major Histocompatibility Complex (MHC) molecules loaded with antigens from antigen-presenting cells (APCs). This acquisition, often called cross-dressing, allows the recipient cell to effectively present the acquired antigen, thereby enhancing or modifying the overall immune response.
The process is also a major factor in immune regulation and the tuning of activation thresholds. For instance, NK cells and T cells can use trogocytosis to rapidly adjust their sensitivity by acquiring or shedding activating or inhibitory receptors from neighboring cells. By stripping inhibitory ligands from a target, the effector cell can enhance its own cytotoxic potential, while the acquisition of activating ligands can paradoxically lead to the NK cell becoming hyporesponsive.
The transfer of membrane components can also impact the fitness and survival signals of both the recipient and donor cells. The gain of certain surface molecules can activate survival pathways in the recipient cell, whereas the stripping of necessary receptors from the donor cell can impair its function or potentially initiate cell death. Trogocytosis is also critical in regulating T cell differentiation and various homeostatic responses across the body.
Implications for Infection and Cancer
Certain pathogens, such as the amoeba Entamoeba histolytica, use trogocytosis to directly damage and kill host cells by actively removing pieces of the membrane. Pathogens can also acquire host proteins through this process to enable immune evasion.
In cancer, trogocytosis presents a significant challenge to the immune system and to modern therapies. Tumor cells can exploit this process to evade immune detection by stripping important surface molecules, such as MHC molecules or checkpoint proteins like PD-L1, from immune cells. This action effectively helps the cancer cell “hide” from surveillance and dampen anti-tumor responses.
Conversely, immune cells like macrophages and NK cells can leverage trogocytosis to attack and kill tumor cells, a process sometimes referred to as trogoptosis. However, in the context of immunotherapy, particularly with Chimeric Antigen Receptor (CAR) T-cell therapy, trogocytosis can lead to therapeutic resistance. CAR T-cells remove tumor antigens like CD19 or CD22 from the cancer cell surface, which allows the tumor cell to escape destruction or causes the CAR T-cells to attack each other in a phenomenon called fratricide.