ArticleMolecular & cellular proteomics : MCP2019
Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behcet's Disease-associated HLA-B*51 Peptidome.
Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Analysis of the different subpeptidomes presented by the HLA class I molecules of the B7 supertype.Cellular immunology · 2023Pooled it
- Review
- Exploring the Involvement ofLife (Basel, Switzerland) · 2026Review
- Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- Biology of HLA class I associated inflammatory diseases.Best practice & research. Clinical rheumatology · 2024Review
- Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions.Frontiers in cell and developmental biology · 2024Article
- Behçet's disease risk-variant HLA-B51/ERAP1-Hap10 alters human CD8 T cell immunity.Annals of the rheumatic diseases · 2022Article
- ERAP1 binds peptide C-termini of different sequences and/or lengths by a common recognition mechanism.Immunobiology · 2021Article
- ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29.Frontiers in immunology · 2021Article
- The Impact of the 'Mis-Peptidome' on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response.International journal of molecular sciences · 2020Review
- HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis.Cells · 2020Article
- Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2).Molecular & cellular proteomics : MCP · 2020Article
- Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade.Journal for immunotherapy of cancer · 2020Article
- The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease.Frontiers in immunology · 2020Article
- Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis.Molecular & cellular proteomics : MCP · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to be loaded onto HLA molecules, including the main risk factor for Behçet's disease HLA-B*51. ERAP1 is also a risk factor among HLA-B*51-positive individuals, whereas no association is known with ERAP2. This study addressed the mutual relationships between both enzymes in the processing of an HLA-bound peptidome, interrogating their differential association with Behçet's disease. CRISPR/Cas9 was used to generate knock outs of ERAP1, ERAP2 or both from transfectant 721.221-HLA-B*51:01 cells. The surface expression of HLA-B*51 was reduced in all cases. The effects of depleting each or both enzymes on the B*51:01 peptidome were analyzed by quantitative label-free mass spectrometry. Substantial quantitative alterations of peptide length, subpeptidome balance, N-terminal residue usage, affinity and presentation of noncanonical ligands were observed. These effects were often different in the presence or absence of the other enzyme, revealing their mutual dependence. In the absence of ERAP1, ERAP2 showed similar and significant processing of B*51:01 ligands, indicating functional redundancy. The high overlap between the peptidomes of wildtype and double KO cells indicates that a large majority of B*51:01 ligands are present in the ER even in the absence of ERAP1/ERAP2. These results indicate that both enzymes have distinct, but complementary and partially redundant effects on the B*51:01 peptidome, leading to its optimization and maximal surface expression. The distinct effects of both enzymes on the HLA-B*51 peptidome provide a basis for their differential association with Behçet's disease and suggest a pathogenetic role of the B*51:01 peptidome.
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