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Journal article

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

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-022-31160-3

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Role:
Author
ORCID:
0000-0002-1641-4107
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Role:
Author
More by this author
Role:
Author
ORCID:
0000-0002-2163-8746
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Role:
Author
ORCID:
0000-0002-5299-1104
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Role:
Author
ORCID:
0000-0001-9523-0586



Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
13
Issue:
1
Article number:
3460
Publication date:
2022-06-16
Acceptance date:
2022-06-07
DOI:
EISSN:
2041-1723
Pmid:
35710644


Language:
English
Keywords:
Pubs id:
1264434
Local pid:
pubs:1264434
Deposit date:
2022-09-19

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