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PXD059637-1

PXD059637 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDNGR-1/CLEC9A signaling limits cDC1 activation to optimize crosspresentation of dead cell antigens
DescriptionInnate immune receptors induce activation of conventional dendritic cells (cDCs) and enhance antigen (cross-)presentation, favoring immune responses. DNGR-1 (CLEC9A), a receptor expressed by type 1 cDCs (cDC1s) and implicated in immunity to viruses and cancers, recognizes F-actin exposed on dead cell remnants and promotes cross-presentation of associated antigens. Here, we show that DNGR-1 does not trigger cDC1 activation, in part by recruiting phosphatase SHIP1, a process governed by a single amino acid adjacent to the signaling motif of the receptor. Substituting this residue converts DNGR-1 into an activating receptor but decreases its induction of cross-presentation of dead cell-associated antigens. Interestingly, introducing the reverse mutation into related receptor Dectin-1 impairs its activation capacity while enhancing its ability to promote cross-presentation. These findings reveal an unexpected functional trade-off in receptor signaling and suggest that DNGR-1 has evolved to prioritize antigen cross-presentation over cellular activation, possibly to minimize inflammatory responses to dead cells.
HostingRepositoryPRIDE
AnnounceDate2025-10-28
AnnouncementXMLSubmission_2025-10-28_07:23:22.011.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMark Skehel
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-01-10 07:37:51ID requested
12025-10-28 07:23:22announced
Publication List
10.1038/S44318-025-00620-Z;
Keyword List
submitter keyword: Mouse, dendritic cell, lc-ms/ms, innate immune receptor
Contact List
Caetano Reis e Sousa
contact affiliationImmunobiology Laboratory, The Francis Crick Institute, London, UK
contact emailcaetano@crick.ac.uk
lab head
Mark Skehel
contact affiliationFrancis Crick Institute
contact emailskehelm@crick.ac.uk
dataset submitter
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Dataset FTP location
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