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PXD020750

PXD020750 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn integrated genomic, proteomic and immunopeptidomic approach to discover treatment-induced neoantigens
DescriptionAll nucleated mammalian cells express major histocompatibility complex (MHC) proteins that present peptides on cell surfaces for immune surveillance. These MHC-presented peptides (pMHC) can convey non-self antigens derived from pathogens or mutations to amount T-cell responses. Alterations in tumor-specific antigens – particularly mutation-bearing peptides (neoantigens) presented by MHC — can serve as potent substrates for anti-tumor immune responses. Here we employed an integrated genomic and proteomic antigen discovery strategy aimed at measuring interferon gamma (IFN-γ) induced alterations to antigen presentation, using a lymphoma cell line. IFN-γ treatment resulted in a set of differentially expressed proteins (2 % of all quantified proteins) including components of antigen presentation machinery or interferon signaling pathways. In addition, several proteasome subunits were found to be modulated, consistent with previous reports of immunoproteasome induction by IFN-γ exposure. This finding suggests that a modest proteomic response to IFN-γ could create larger alteration to cells antigen repertoires. Accordingly, by surveying immunopeptides, distinct peptide repertoires were exclusively observed in the IFN-γ induced samples. Furthermore, an additional set of presented peptides distinguished control and the IFN-γ samples by their altered relative abundances including neoantigens. Accordingly, we developed a classification system to distinguish peptides which are differentially presented due to altered expression from novel peptides resulting from changes in antigen processing. Taken together, these data demonstrate that IFN-γ can re-shape antigen repertoires by identity and by abundance. Extending this approach to models with greater clinical relevance should help develop strategies by which immunopeptide repertoires are intentionally reshaped to improve endogenous or vaccine-induced anti-tumor immune responses and potentially anti-viral immune responses.
HostingRepositoryPRIDE
AnnounceDate2021-09-09
AnnouncementXMLSubmission_2021-09-09_07:29:31.412.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNiclas Olsson
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListcysteinylation (disulfide with free L-cysteine); phosphorylated residue; monohydroxylated residue; deamidated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-08-05 10:00:28ID requested
12021-09-09 07:29:32announced
Publication List
Olsson N, Heberling ML, Zhang L, Jhunjhunwala S, Phung QT, Lin S, Anania VG, Lill JR, Elias JE, An Integrated Genomic, Proteomic, and Immunopeptidomic Approach to Discover Treatment-Induced Neoantigens. Front Immunol, 12():662443(2021) [pubmed]
Keyword List
submitter keyword: Human, MHC, antigen presentation, interferon gamma, Orbitrap
Contact List
Joshua E Elias
contact affiliationChan Zuckerberg Biohub, Stanford, CA, USA
contact emailjosh.elias@czbiohub.org
lab head
Niclas Olsson
contact affiliationStanford University
contact emailnic.e.olsson@gmail.com
dataset submitter
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Dataset FTP location
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