Abstract
Communication between cells is essential for multicellular life. During cognate immune interactions, T cells communicate with antigen-presenting cells (APC) via direct cell–cell contact or the release of molecules and vesicles containing T cell messages. A wide variety of mechanisms have been reported and among them a process called “trogocytosis” has traditionally been thought to be the fastest way to directly transfer membrane portions containing intact proteins from one cell to another; however, the mechanism is unverified. Trogocytosis has been distinguished from the generation of extracellular vesicles (EVs), a term that encompasses exosomes and microvesicles, as EVs are released via a contact-independent manner and are suggested to potentially send molecular messages over a distance. However, some previous reports regarding EVs in T cells may be misleading in terms of explaining their cellular origins. In addition, there is little evidence on how EVs are generated from T cells in vivo and function to regulate complex immune responses. A recent work demonstrated that T cell microvilli—thin and finger-like membrane protrusions—are highly fragile and easily separated as membrane particles by trogocytosis, forming a new class of EVs. Surprisingly, released T cell microvilli-derived particles act as vectors, transmitting T cell messages to cognate APCs. This review focuses on how T cell microvilli vesicles are connected with immune regulation mechanisms discovered previously.
Highlights
Information exchange between T cells and cognate antigen-presenting cells (APCs) dictates the character and scope of immune responses
A more striking point is that microvilli are selectively enriched with the membrane sorting complexes such as arrestin domain-containing protein 1 (Arrrdc1), TSG101, and Vps4, which are well-known to mediate microvesicle budding at the cell surface and are known to be involved in the immunological synapse (IS) [3, 43, 44]
Choudhuri et al demonstrated that TCR-enriched microvesicles are released from the central supramolecular activation clusters (cSMAC), we identified that TCR-enriched T cell microvilli particles are highly separated during T cell kinapses, suggesting that the generation of TCR-enriched vesicles are not restricted to the cSMAC, but can be separated from microvilli during T cell activation
Summary
Information exchange between T cells and cognate antigen-presenting cells (APCs) dictates the character and scope of immune responses. Over two decades before the IS was discovered, scientists made surprising in vitro and in vivo observations; proteins thought to be specific for one cell type were found in small amounts on the surfaces of other cell types [6,7,8]. This process has been referred as “absorption” [9], “internalization” [10], or “trogocytosis” [11, 12] (from the ancient Greek “trogo,” meaning “gnaw” or “nibble”) and has characteristics distinct from enzymemediated cleavage or exosomal transfer [12, 13]. We focus on the T cell microvilli and their roles in molecular and cellular aspects, especially in relation to the IS and TCR clusters, trogocytosis, membrane nanotubes, and EVs
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