PXD042469

PXD042469 is an original dataset announced via ProteomeXchange.

Title	Viral control by a unique cytotoxic SARS-CoV-2 spike protein-specific CD4+ T cell population
Description	Little is known of the role of cytotoxic CD4+ T-cells (CTLs) in the control of human viral replication. Here, we investigate CD4+ T-cell responses to three immunodominant SARS-CoV-2 epitopes identified in our study cohort, and evaluate cytotoxic activity and antiviral cytokine production in response to virus infected cells together with changes in the transcriptome and proteome of CD4+ CTLs. We found S866-880-specific CD4+ T-cells exhibit the highest cytotoxicity, which correlated with the strongest anti-viral efficacy; moreover, this was independent of TCR usage or IL-2 production. CD4+ CTLs exhibited distinct signalling and cytotoxic pathways compared to classical CD8+ T-cells, with increased expression of GZMM and GZMK, together with chemokines and tissue homing receptors promoting migration. Furthermore, CD4+ CTLs showed decreased expression of KYNU, IDO1 and SOD2 implicating a dampening of Treg-mediated suppression of CD4+ effector function. We also found diverse T cell receptor (TCR) usage including an unexpected high level of public TCR usage among all three epitope specific T cells; however, this did not correlate with cytotoxicity or functional avidity. Our study suggested unique features of cytotoxic CD4+ T-cells, implicating distinct functional pathways, which could play an important role in viral control of memory T cell responses induced by infection or vaccination.
HostingRepository	PRIDE
AnnounceDate	2025-08-15
AnnouncementXML	Submission_2025-08-15_04:58:48.631.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: NCBITaxon:2697049; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-24 03:34:15	ID requested
⏵ 1	2025-08-15 04:58:49	announced

Dataset with its publication pending

submitter keyword: Human, epitotpes, SARS-CoV-2, CD4+ Tcells, LC-MS/NS

Tao Dong
contact affiliation	Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Oxford, U.K.; 3MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford; Oxford, U.K.
contact email	tao.dong@ndm.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	Target Discovery Institute, NDMRB
contact email	iolanda.vendrell@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042469
     1. Label: PRIDE project
     2. Name: Viral control by a unique cytotoxic SARS-CoV-2 spike protein-specific CD4+ T cell population