PXD066752

PXD066752 is an original dataset announced via ProteomeXchange.

Title	ERAP1 allotypes 2 and 10 differentially regulate the immunopeptidome of melanocytes
Description	Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a polymorphic enzyme that shapes the peptide repertoire presented by MHC class I molecules and can regulate adaptive immune responses in cancer and autoimmunity. Common missense polymorphisms in ERAP1 modulate its activity and are found in specific allotypes in humans. ERAP1 allotypes are linked to predisposition to HLA-associated inflammatory diseases. ERAP1 allotypic variation has been correlated with the development of psoriasis and Bechet’s disease, through the generation of specific CD8+ T cell populations targeting disease-specific HLAs. Given the established broad effects of ERAP1 activity on the cellular immunopeptidome, we hypothesized that ERAP1 allotypic variation may lead to broad immunopeptidome shifts that underlie antigenic responses. To test this hypothesis, we generated two A375 melanoma cell lines, each one expressing one of the most common, disease-associated, ERAP1 allotypes, namely allotypes 2 or 10. Comparison of the immunopeptidome of these two cell lines showed only minor differences in peptide sequences presented but extensive changes in abundance that included alterations in length distribution, binding affinity and sequence motifs. Our results suggest that enzymatic differences between ERAP1 allotypes are reflected primarily on the quantitative composition of the cellular immunopeptidome. These quantitative changes may constitute a mechanism that underlies ERAP1-allotypic associations with HLA-associated autoimmunity and variable anti-tumor responses.
HostingRepository	PRIDE
AnnounceDate	2025-11-04
AnnouncementXML	Submission_2025-11-04_06:47:01.851.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Samiotaki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	cysteinylation (disulfide with free L-cysteine); acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-30 03:35:50	ID requested
⏵ 1	2025-11-04 06:47:02	announced

10.1111/IMM.70056;

submitter keyword: ERAP1, Allotypes, Immunopeptidomics

Efstratios Stratikos
contact affiliation	Department of Chemistry, National and Kapodistrian University of Athens, 15784 Zografou, Greece
contact email	estratikos@chem.uoa.gr
lab head
Martina Samiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066752
     1. Label: PRIDE project
     2. Name: ERAP1 allotypes 2 and 10 differentially regulate the immunopeptidome of melanocytes