2026-05-16T22:10:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/128302024-10-31T11:50:38Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Lorente, Elena
author
Redondo-Anton, Jennifer
author
Martín-Esteban, Adrian
author
Guasp, Pablo
author
Barnea, Eilon
author
Lauzurica, Pilar
author
Admon, Arie
author
López de Castro, José A
funder
Ministerio de Ciencia e Innovación (España)
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
funder
Israel Science Foundation
funder
Fundación Ramón Areces
2021-04-29T11:29:38Z
2021-04-29T11:29:38Z
2019
Mol Cell Proteomics. 2019;18(11):2298-2309.
10.1074/mcp.RA119.001710
1535-9484
Molecular & cellular proteomics
31530632
http://hdl.handle.net/20.500.12105/12830
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 wild-type 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, and aliphatic/aromatic ones decreased in the ERAP2 knockout. Other peptide positions were also affected. Because most of the non-B*27 MHC-I molecules associated with AS risk 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, thus affecting the peptidomes of AS-associated MHC-I molecules.
eng
Ankylosing Spondylitis
ERAP2
Enzyme Mechanisms
HLA-B*40
Immunology
Inflammation
Label-Free Quantification
Peptidomics
Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis.
journal article
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