Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/10488
Título
Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2).
Autor(es)
Lorente, Elena ISCIII | Gomez Fontela, Miguel ISCIII | Barnea, Eilon | Martin-Galiano, Antonio Javier ISCIII | Mir-Gerrero, Carmen ISCIII | Galocha, Begoña ISCIII | Admon, Arie | Lauzurica, Pilar ISCIII | Lopez, Daniel ISCIII
Fecha de publicación
2020-06
Cita
Mol Cell Proteomics. 2020 Jun;19(6):994-1004.
Idioma
Inglés
Tipo de documento
journal article
Resumen
The HLA-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with AS, a chronic inflammatory spondyloarthropathy. This study examined the effect of ERAP2 in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones, and the peptides were identified using high-throughput mass spectrometry analyses. The relative abundance of a thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in the presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of the antigen-binding site of the HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and PΩ positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from Campylobacter jejuni These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease.
Descripción
The mass spectrometry data have been deposited to the MassIVE repository (http://massive.ucsd.edu) with the data set identifier MSV000084718.
Versión en línea
DOI
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