PXD063349

PXD063349 is an original dataset announced via ProteomeXchange.

Title	Inhibitory TIGIT signalling is dependent on activating T cell receptor signalling
Description	TIGIT is an immune checkpoint receptor that can signal via its intracellular inhibitory motifs to inhibit T cells, though the mechanisms remain poorly defined. To elucidate inhibitory signalling interactors of TIGIT, proximity proteomics was employed in model Jurkat T cells expressing TIGIT fused to APEX2. This identified several ligation-specific TIGIT interactors, including proteins involved in signalling (Grb2 and SOS1), cytoskeletal (CD2AP and SdcBP), and endocytic processes (IST1 and SNX3). A TIGIT mutant incapable of signalling via its inhibitory motifs prevented the recruitment of these proteins, indicating inhibitory signalling-specific engagement of these pathways. Furthermore, TIGIT engagement with these pathways, in addition to its phosphorylation and internalisation, was dependent on T cell activation as well as TIGIT ligation. Collectively, these findings demonstrate that TIGIT inhibitory signalling is restricted to activated T cells, indicating a regulatory mechanism that limits inhibition to when functionally required.
HostingRepository	PRIDE
AnnounceDate	2025-05-14
AnnouncementXML	Submission_2025-05-14_05:36:31.948.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	William Zammit
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-25 11:50:31	ID requested
⏵ 1	2025-05-14 05:36:32	announced

10.1101/2025.05.08.652881;

submitter keyword: proximity proteomics, APEX2, signalling, T cells,TIGIT

Jonathan D. Worboys
contact affiliation	University of Manchester
contact email	jonathan.worboys@manchester.ac.uk
lab head
William Zammit
contact affiliation	University of Manchester
contact email	william.zammit@manchester.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063349
     1. Label: PRIDE project
     2. Name: Inhibitory TIGIT signalling is dependent on activating T cell receptor signalling