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

Céspedes PF., Jainarayanan A., Fernández-Messina L., Valvo S., Saliba DG., Kurz E., Kvalvaag A., Chen L., Ganskow C., Colin-York H., Fritzsche M., Peng Y., Dong T., Johnson E., Siller-Farfán JA., Dushek O., Sezgin E., Peacock B., Law A., Aubert D., Engledow S., Attar M., Hester S., Fischer R., Sánchez-Madrid F., Dustin ML.

AbstractThe 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.

DOI

10.1038/s41467-022-31160-3

Type

Journal article

Journal

Nature Communications

Publisher

Springer Science and Business Media LLC

Publication Date

12/2022

Volume

13

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