In a process called “trogocytosis,” proteins are transferred at the cell-surface interface between different cells. A prominent example happens in immune cells, in which peptide-major histocompatibility complexes (MHCs) are exchanged from antigen-presenting cells (APCs) to T cells. Recently, bidirectional transfer has also been observed in mice, with APCs being able to acquire the T cell receptor.
New findings published in Nature Communications have uncovered a molecular mechanism by which lymphocytes communicate with APCs. The work, led by Gwangju Institute of Science and Technology in South Korea highlight the role of the T cell microvilli, a structure on the cell surface.
“Lymphocytes contain abundant flexible projections termed microvilli, the inside of which contain many parallel bundles of actin filaments that extend the cell membrane in the form of a finger,” the team noted in their paper. “In this study, we observe that single T cell contacts with APCs occur through microvillar extensions, which appear to serve as locations for sequestration of immunologically important molecules, including TCR complexes, costimulatory and adhesion molecules, and various cytokines.”
From electron microscopy and fluorescent imaging on Jurkat T cells, the team observed that T cells generated particles originating from microvilli upon TCR stimulation. Further investigation revealed that at all stages of T cell activation, the microvilli carries T cell receptors (TCR) that, in the process of trogocytosis, are released as large, TCR-enriched, T cell microvilli particles.
Mass spectrometric analyses of these particles using LC-MS/MS showed many proteins involved in direct plasma-membrane budding complexes, such as Arrdc1, TSG101, and Vps4 a/b. The particles also exclusively contained important T cell proteins, including the TCR complex and other costimulatory molecules. Further experiments showed that the particles were able to interact and activate dendritic cells. Altogether, it appears that these microvilli particles are a means of transferring key proteins from the T cell microvilli to communicate with other immune cells.
“We find that microvilli are separated from the T cell body by the combined action of two independent mechanisms (trogocytosis and membrane budding) and are deposited at the surface of cognate APCs, thereby potentially acting as an effective means of delivering T cell messages to cognate APCs,” the team concluded.
“Consistent with this potential role, these T cell microvilli-derived particles (TMP) are independently capable of activating cognate dendritic cells (DC). Therefore, our findings suggest that T cell microvilli might serve as “immunological synaptosomes” with TMPs as a class of membrane vesicles serving as conveyors of T cell messages or traits to cognate APCs.”
Image: Confocal fluorescent microscopy depicts Jurkat T cells generating V5G+ microvilli particles. Image courtesy of Chang-Duk Jun and Springer Nature.