PXD005502

PXD005502 is an original dataset announced via ProteomeXchange.

Title	HLA B-27 rats peptidome - The HLA-B27 peptidome in vivo in spondyloarthritis-susceptible HLA-B27 transgenic rats and the effect of ERAP1 deletion
Description	HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large-scale quantitative mass-spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of ERAP1, which reduced ERAP1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of ERAP1 affected approximately one third of the B27 peptidome, but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of ERAP1. Deletion on ERAP1 was permissive for the AS-like phenotype. Deletion of ERAP1 increased mean peptide length, and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser or Lys. The presence of ERAP1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:33:58.066.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dganit Melamed Kadosh
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-12-05 05:53:18	ID requested
1	2017-02-13 08:31:40	announced
⏵ 2	2024-10-22 04:33:59	announced	2024-10-22: Updated project metadata.

10.1074/mcp.M116.066241;

Barnea E, Melamed Kadosh D, Haimovich Y, Satumtira N, Dorris ML, Nguyen MT, Hammer RE, Tran TM, Colbert RA, Taurog JD, Admon A, , in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion. Mol Cell Proteomics, 16(4):642-662(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Transgenic rats, HLA-B27, Peptidome, Ankylosing Spondylitis,Human Leukocytes Antigen

Arie Admon
contact affiliation	Technion-Israel Institute of Technology
contact email	admon@tx.technion.ac.il
lab head
Dganit Melamed Kadosh
contact affiliation	Technion
contact email	sdganit@tx.technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005502
     1. Label: PRIDE project
     2. Name: HLA B-27 rats peptidome - The HLA-B27 peptidome in vivo in spondyloarthritis-susceptible HLA-B27 transgenic rats and the effect of ERAP1 deletion