PXD006215

PXD006215 is an original dataset announced via ProteomeXchange.

Title	The Behçet’s Disease associated Hap10 variant of ERAP1 generates a low affinity HLA-B*51 peptidome through differential processing of two subpeptidomes
Description	HLA-B*51, the main risk factor for Behçet’s disease (BD), binds two main subpeptidomes consisting of low affinity peptides with Ala as their second amino acid and higher affinity peptides with Pro at this position. A low activity variant of ERAP1, Hap10, is uniquely associated with BD susceptibility in epistasis with HLA-B*51. The peptidome presented by HLA-B*51:08 in a cell line expressing Hap10 was compared with the HLA-B*51:01 peptidome from a cell line expressing higher activity variants of ERAP1. The differences due to ERAP1 could be clearly distinguished from those due to subtype polymorphism. The latter should not affect disease susceptibility, since both HLA-B*51 subtypes are associated with BD. In the lower activity, BD-associated, ERAP1 context longer peptides were generated, the Pro2 subpeptidome was significantly reduced, and the Ala2 subpeptidome was correspondingly increased and showed a higher frequency of ERAP1-susceptible P1 residues. These effects are readily explained by the low activity of the disease-associated Hap10 variant, and together resulted in a significantly altered HLA-B*51 peptidome of lower affinity. The differences between both B*51 subtypes affected residue usage at various internal positions of the peptide ligands, including P3, where B*51:01 showed preference for aromatic residues whereas B*51:08 preferred smaller and polar ones. The profound effects of the BD-associated Hap10 haplotype on the nature and affinity of HLA-B*51/peptide complexes could significantly alter T-cell and NK cell recognition, providing a basis for the joint association of ERAP1 and HLA-B*51 to BD.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:02:01.584.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	2017-03-30 03:10:31	ID requested
1	2018-10-24 14:31:38	announced
⏵ 2	2024-10-22 04:02:02	announced	2024-10-22: Updated project metadata.

10.1074/jbc.M117.789180;

Guasp P, Barnea E, Gonz, á, lez-Escribano MF, Jim, é, nez-Reinoso A, Regueiro JR, Admon A, L, ó, pez de Castro JA, et's disease-associated variant of the aminopeptidase ERAP1 shapes a low-affinity HLA-B*51 peptidome by differential subpeptidome processing. J Biol Chem, 292(23):9680-9689(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Behçet's disease, ERAP1, HLA-B*51, Antigen processing

Arie Admon
contact affiliation	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. PXD006215
     1. Label: PRIDE project
     2. Name: The Behçet’s Disease associated Hap10 variant of ERAP1 generates a low affinity HLA-B*51 peptidome through differential processing of two subpeptidomes