PXD014804

PXD014804 is an original dataset announced via ProteomeXchange.

Title	Substantial Influence of ERAP2 on the HLA-B*40:02 peptidome. Implications for HLA-B*27-negative ankylosing spondylitis.
Description	HLA-B*40:02 is one of a few Major Histocompatibility Complex class I (MHC-I) molecules associated with ankylosing spondylitis (AS) independently of HLA-B*27. The endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme that process MHC-I ligands and preferentially trims N-terminal basic residues, is also a risk factor for this disease. Like HLA-B*27 and other AS-associated MHC-I molecules, HLA-B*40:02 binds a relatively high percentage of peptides with ERAP2-susceptible residues. In this study the effects of ERAP2 depletion on the HLA-B*40:02 peptidome were analyzed. ERAP2 protein expression was knocked out by CRISPR in the transfectant cell line C1R-B*40:02 and the differences between the peptidomes from the wildtype and ERAP2-KO cells were determined by label-free quantitative comparisons. The qualitative changes dependent on ERAP2 affected about 5% of the peptidome, but quantitative changes in peptide amounts were much more substantial, reflecting a significant influence of this enzyme on the generation/destruction balance of HLA-B*40:02 ligands. As in HLA-B*27, a major effect was on the frequencies of N-terminal residues. In this position basic and small residues were increased in the absence of ERAP2 and aliphatic/aromatic residues were increased in the presence of the enzyme. Since most of the non-B*27 MHC-I molecules associated with AS risk also bind a relatively high percentage of peptides with N-terminal basic residues we hypothesize that the non-epistatic association of ERAP2 with AS might be related to the processing of peptides with these residues bound by AS-associated MHC-I molecules.
HostingRepository	PRIDE
AnnounceDate	2019-09-25
AnnouncementXML	Submission_2019-09-25_08:43:45.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	2019-07-29 04:37:46	ID requested
⏵ 1	2019-09-25 08:43:47	announced

Lorente E, Redondo-Ant, ó, n J, Mart, í, n-Esteban A, Guasp P, Barnea E, Lauzurica P, Admon A, L, ó, pez de Castro JA, Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis. Mol Cell Proteomics, 18(11):2298-2309(2019) [pubmed]

submitter keyword: ERAP2,HLA-B*40:02 peptidome, HLA-B*27, ankylosing spondylitis

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. PXD014804
     1. Label: PRIDE project
     2. Name: Substantial Influence of ERAP2 on the HLA-B*40:02 peptidome. Implications for HLA-B*27-negative ankylosing spondylitis.