PXD011766

PXD011766 is an original dataset announced via ProteomeXchange.

Title	Editing the immunopeptidome of melanoma cells using a potent inhibitor of ER aminopeptidase 1
Description	The efficacy of cancer immunotherapy, including treatment with immune-checkpoint inhibitors, is often limited by ineffective presentation of antigenic peptides that can elicit T-cell mediated anti-tumor cytotoxic responses. Therefore, manipulating antigen presentation is an emerging approach for enhancing the immunogenicity of tumors in immunotherapy settings. ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that trims peptides that can bind onto MHC class I molecules (MHC-I). We hypothesized that pharmacologically inhibiting ERAP1 in cells can regulate the global cellular immunopeptidome. To test this hypothesis, we treated the A375 melanoma cell line with a recently developed potent ERAP1 inhibitor and analyzed the presented MHC-I peptide repertoire by isolating MHC-I, eluting the bound peptides and identifying them using capillary chromatography and tandem mass spectrometry. Although the inhibitor did not negatively affect overall MHC-I presence on the cell surface, it induced significant changes on the presented peptidomes, both at the qualitative and quantitative levels. Specifically, inhibitor treatment altered about half of the total 3204 identified peptides and about one third of the peptides predicted to be good ligands for MHC-I, affected length and sequence without however interfering with basic binding motifs. Strikingly, the inhibitor enhanced overall MHC-I binding affinity by reducing presentation of sub-optimal long peptides and generating many high-affinity 9-12mers, suggesting that baseline ERAP1 activity in this cell line is destructive for many potential epitopes. Our results suggest that chemical inhibition of ERAP1 is a valid approach for manipulating the immunopeptidome of cancer and autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2019-06-25
AnnouncementXML	Submission_2019-06-25_02:07:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eilon Barnea
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-20 05:29:34	ID requested
⏵ 1	2019-06-25 02:07:50	announced

Koumantou D, Barnea E, Martin-Esteban A, Maben Z, Papakyriakou A, Mpakali A, Kokkala P, Pratsinis H, Georgiadis D, Stern LJ, Admon A, Stratikos E, Editing the immunopeptidome of melanoma cells using a potent inhibitor of endoplasmic reticulum aminopeptidase 1 (ERAP1). Cancer Immunol Immunother, 68(8):1245-1261(2019) [pubmed]

submitter keyword: immunopeptidome, ERAP1, inhibitor

Arie Admon
contact affiliation	Faculty of Biology, Technion - Israel Institute of Technology
contact email	admon@technion.ac.il
lab head
Eilon Barnea
contact affiliation	Technion
contact email	eilonb@tx.technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011766
     1. Label: PRIDE project
     2. Name: Editing the immunopeptidome of melanoma cells using a potent inhibitor of ER aminopeptidase 1