PXD012728

PXD012728 is an original dataset announced via ProteomeXchange.

Title	Direct quantification of viral epitope abundance reveals the importance of direct and cross-presentation in driving CTL responses during influenza infection
Description	The magnitude of CD8+ T lymphocyte (CTL) responses to infection is a function of the available naïve T cell repertoire, combined with the context and duration of antigen presentation. Whilst T cell repertoires are relatively easily studied, the context and abundance of epitopes presented on infected cells and dendritic cells (DCs) and their subsequent impact on CTL responses are generally poorly understood. Using quantitative mass spectrometry, we identified and quantified the abundance of 21 class 1 Major Histocompatibility Complex molecule (MHCI)-restricted influenza A virus (IAV)-derived peptides following either direct presentation or cross-presentation. All identified peptides, including seven novel epitopes, elicited T cell responses in infected C57BL/6 mice. Quantitation of IAV epitopes displayed via direct presentation showed a maintenance of relative epitope abundance across distinct cell types, reflecting common antigen processing mechanisms. Comparison of epitope levels displayed via direct presentation and cross-presentation revealed a broad range of directly presented epitope abundances, which was normalised during cross-presentation. Further, we observed a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drove optimal nucleoprotein (NP)366-374 presentation, while cross-presentation was optimal for acid polymerase (PA)224-233 presentation. This study provides a detailed dissection of viral pMHCI abundance after infection and reveals the importance of both direct and cross-presentation in driving dominant CTL responses. The study also demonstrates how empirical assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
HostingRepository	PRIDE
AnnounceDate	2019-07-02
AnnouncementXML	Submission_2019-07-03_00:18:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nathan Croft
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-15 03:24:12	ID requested
1	2019-07-02 07:38:20	announced
⏵ 2	2019-07-03 00:18:08	announced	Updated publication reference for PubMed record(s): 31253788.

Wu T, Guan J, Handel A, Tscharke DC, Sidney J, Sette A, Wakim LM, Sng XYX, Thomas PG, Croft NP, Purcell AW, La Gruta NL, Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses. Nat Commun, 10(1):2846(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: MHC, peptide, MRM, SRM, influenza

Anthony Purcell
contact affiliation	Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
contact email	anthony.purcell@monash.edu
lab head
Nathan Croft
contact affiliation	Monash University
contact email	nathan.croft@monash.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/07/PXD012728

PRIDE project URI

• PRIDE
  1. PXD012728
     1. Label: PRIDE project
     2. Name: Direct quantification of viral epitope abundance reveals the importance of direct and cross-presentation in driving CTL responses during influenza infection