PXD000394

PXD000394 is an original dataset announced via ProteomeXchange.

Title	Mass spectrometry of HLA-I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation
Description	HLA class I molecules reflect the health state of cells to cytotoxic T-cells by presenting a repertoire of endogenously derived peptides. However, the extent to which the proteome shapes the peptidome is still largely unknown. Here we present a high-throughput mass-spectrometry-based workflow that allows stringent and accurate identification of thousands of such peptides and direct determination of binding motifs. Applying the workflow to seven cancer cell lines and primary cells, yielded more than 22,000 unique HLA peptides across different allelic binding specificities. By computing a score representing the HLA-I sampling density, we show a strong link between protein abundance and HLA-presentation (P<0.0001). When analyzing over-presented proteins - those with at least five-fold higher density score than expected for their abundance – we noticed that they are degraded almost 3 hours faster than similar but non-presented proteins (top 20% abundance class; median half-life 20.8h vs. 23.6h, p<0.0001). This validates protein degradation as an important factor for HLA presentation. Ribosomal, mitochondrial respiratory chain and nucleosomal proteins as particularly well presented. Taking a set of proteins associated with cancer, we compared the predicted immunogenicity of previously validated T-cell epitopes with other peptides from these proteins in our dataset. The validated epitopes indeed tend to have higher immunogenic scores than the other detected HLA peptides, suggesting the usefulness of combining MS-analysis with immunogenesis prediction for ranking and selection of epitopes for therapeutic use.
HostingRepository	PRIDE
AnnounceDate	2016-10-27
AnnouncementXML	Submission_2016-10-27_04:00:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2013-08-02 01:18:53	ID requested
1	2015-01-12 04:11:31	announced
2	2015-06-11 04:47:52	announced	Updated publication reference for PubMed record(s): 25576301.
⏵ 3	2016-10-27 04:00:38	announced	Updated project metadata.

Bassani-Sternberg M, Pletscher-Frankild S, Jensen LJ, Mann M, Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation. Mol Cell Proteomics, 14(3):658-73(2015) [pubmed]

ProteomeXchange project tag: Human Immuno-Peptidome Project (HUPO-HIPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biomedical, Biological

submitter keyword: HLA peptidome, mass spectrometry

Matthias Mann
contact affiliation	Dept. Proteomics and Signal Transduction Max-Planck Institute of Biochemistry Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD000394
     1. Label: PRIDE project
     2. Name: Mass spectrometry of HLA-I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation