T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles

The immunological synapse is a molecular hub that facilitates the delivery of three activation signals, namely antigen, costimulation/corepression and cytokines, from antigen-presenting cells (APC) to T cells. T cells release a fourth class of signaling entities, trans-synaptic vesicles (tSV), to me...

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Bibliographic Details
Authors: Céspedes, Pablo, Jainarayanan, Ashwin, Fernández Messina, Lola María, Valvo, Salvatore, Saliba, David, Kurz, Elke, Kvalvaag, Audun, Chen, Lina, Ganskow, Charity, Colin-York, Huw, Fritzsche, Marco, Peng, Yanchun, Dong, Tao, Johnson, Errin, Siller-Farfán, Jesús, Dushek, Omer, Sezgin, Erdinc, Peacock, Ben, Law, Alice, Aubert, Dimitri, Engledow, Simon, Attar, Moustafa, Hester, Svenja, Fischer, Roman, Sánchez-Madrid, Francisco, Dustin, Michael
Format: article
Publication Date:2022
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/97247
Online Access:https://hdl.handle.net/20.500.14352/97247
Access Level:Open access
Keyword:576
577.2
612.017
T cells
Extracellular signalling molecules
ESCRT
Lymphocyte activation
Biología celular (Biología)
Biología molecular (Biología)
Inmunología
2407 Biología Celular
2415 Biología Molecular
2412 Inmunología
Description
Summary:The immunological synapse is a molecular hub that facilitates the delivery of three activation signals, namely antigen, costimulation/corepression and cytokines, from antigen-presenting cells (APC) to T cells. T cells release a fourth class of signaling entities, trans-synaptic vesicles (tSV), to mediate bidirectional communication. Here we present bead-supported lipid bilayers (BSLB) as versatile synthetic APCs to capture, characterize and advance the understanding of tSV biogenesis. Specifically, the integration of juxtacrine signals, such as CD40 and antigen, results in the adaptive tailoring and release of tSV, which differ in size, yields and immune receptor cargo compared with steadily released extracellular vesicles (EVs). Focusing on CD40L+ tSV as model effectors, we show that PD-L1 trans-presentation together with TSG101, ADAM10 and CD81 are key in determining CD40L vesicular release. Lastly, we find greater RNA-binding protein and microRNA content in tSV compared with EVs, supporting the specialized role of tSV as intercellular messengers.

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