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

Pablo F. Céspedes (), Ashwin Jainarayanan, Lola Fernández-Messina, Salvatore Valvo, David G. Saliba, Elke Kurz, Audun Kvalvaag, Lina Chen, Charity Ganskow, Huw Colin-York, Marco Fritzsche, Yanchun Peng, Tao Dong, Errin Johnson, Jesús A. Siller-Farfán, Omer Dushek, Erdinc Sezgin, Ben Peacock, Alice Law, Dimitri Aubert, Simon Engledow, Moustafa Attar, Svenja Hester, Roman Fischer, Francisco Sánchez-Madrid and Michael L. Dustin ()
Additional contact information
Pablo F. Céspedes: The University of Oxford
Ashwin Jainarayanan: The University of Oxford
Lola Fernández-Messina: Universidad Autónoma de Madrid
Salvatore Valvo: The University of Oxford
David G. Saliba: The University of Oxford
Elke Kurz: The University of Oxford
Audun Kvalvaag: The University of Oxford
Lina Chen: The University of Oxford
Charity Ganskow: The University of Oxford
Huw Colin-York: The University of Oxford
Marco Fritzsche: The University of Oxford
Yanchun Peng: The University of Oxford
Tao Dong: The University of Oxford
Errin Johnson: The University of Oxford
Jesús A. Siller-Farfán: The University of Oxford
Omer Dushek: The University of Oxford
Erdinc Sezgin: Karolinska Institutet
Ben Peacock: NanoFCM, MediCity
Alice Law: NanoFCM, MediCity
Dimitri Aubert: NanoFCM, MediCity
Simon Engledow: The University of Oxford
Moustafa Attar: The University of Oxford
Svenja Hester: The University of Oxford
Roman Fischer: The University of Oxford
Francisco Sánchez-Madrid: Universidad Autónoma de Madrid
Michael L. Dustin: The University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31160-3

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DOI: 10.1038/s41467-022-31160-3

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