PXD007679

PXD007679 is an original dataset announced via ProteomeXchange.

Title	Allele-specific alterations in the peptidome underlie the joint association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy
Description	Birdshot chorioretinopathy (BSCR) is a rare inflammatory eye disease very strongly associated with HLA-A*29:02, with >95% of patients carrying this allele. BSCR is also associated with endoplasmic reticulum aminopeptidase (ERAP)2, an enzyme involved in processing HLA class I ligands. We analyzed the relationship between both risk factors, to address the basis for their joint association with BSCR. Label-free quantitative mass spectrometry was used to characterize the effects of ERAP2 on the A*29:02-bound peptidome. An ERAP2-negative cell line was transduced with lentiviral constructs containing GFP or GFP-ERAP2, and the A*29:02 peptidomes from mock- and ERAP2-transduced cells were compared. A similar analysis was performed with two A*29:02-positive, ERAP1-concordant, cell lines differing in their expression or not of ERAP2. In both comparisons the presence of ERAP2 affected the following features of the A*29:02 peptidome: 1) Length, with increased amounts of peptides >9-mers, and 2) N-terminal residues, with less ERAP2-susceptible and more hydrophobic ones. The paradoxical effects on peptide length suggest that unproductive binding to ERAP2 might protect some peptides from over-trimming. The influence on N-terminal residues is consistent with a double effect of ERAP2: a direct one on peptide trimming and improved processing in concert with ERAP1. The alterations in the A*29:02 peptidome suggest that the association of ERAP2 with BSCR is through its effects on peptide processing. These differ from those on the ankylosing spondylitis-associated HLA-B*27. Thus, ERAP2 alters the peptidome of distinct HLA molecules as a function of their specific binding preferences, influencing different pathological outcomes in an allele-dependent way.
HostingRepository	PRIDE
AnnounceDate	2018-05-17
AnnouncementXML	Submission_2018-05-21_03:40:14.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	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-06 07:36:50	ID requested
1	2018-05-17 07:44:49	announced
⏵ 2	2018-05-21 03:40:15	announced	Updated publication reference for PubMed record(s): 29769354.

Sanz-Bravo A, Mart, í, n-Esteban A, Kuiper JJW, Garc, í, a-Peydr, ó M, Barnea E, Admon A, L, ó, pez de Castro JA, Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy. Mol Cell Proteomics, 17(8):1564-1577(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: HLA-A*29:02, Endoplasmic Reticulum Aminopeptidase 2 (ERAP2), Birdshot Chorioretinopathy

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. PXD007679
     1. Label: PRIDE project
     2. Name: Allele-specific alterations in the peptidome underlie the joint association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy