ArticleMolecular & cellular proteomics : MCP2014
Peptide handling by HLA-B27 subtypes influences their biological behavior, association with ankylosing spondylitis and susceptibility to endoplasmic reticulum aminopeptidase 1 (ERAP1).
Article in Molecular & cellular proteomics : MCP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
The trial behind it
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Association Between Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Polymorphisms and Risk of Ankylosing Spondylitis: A Meta-analysis.Medical science monitor : international medical journal of experimental and clinical research · 2017Pooled it
- Association between IL23R and ERAP1 polymorphisms and sacroiliac or spinal MRI inflammation in spondyloarthritis: DESIR cohort data.Arthritis research & therapy · 2019Trial
- Emerging biochemical, microbial and immunological evidence in the search for why HLA-BCell chemical biology · 2025Review
- ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses Cross-Reactive to Self-Epitopes.International journal of molecular sciences · 2023Article
- Upregulation of Unfolded Protein Response and ER Stress-Related IL-23 Production in M1 Macrophages from Ankylosing Spondylitis Patients.Inflammation · 2022Article
- Joint together: The etiology and pathogenesis of ankylosing spondylitis.Frontiers in immunology · 2022Review
- Aberrant antigen processing and presentation: Key pathogenic factors leading to immune activation in Ankylosing spondylitis.Seminars in immunopathology · 2021Review
- 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
- Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy.Molecular & cellular proteomics : MCP · 2018Article
- An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes.Scientific reports · 2018Article
- Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity.Frontiers in immunology · 2018Review
- How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins.Frontiers in immunology · 2018Review
- The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis.Clinical and experimental immunology · 2017Review
- Pathogenesis of ankylosing spondylitis - recent advances and future directions.Nature reviews. Rheumatology · 2017Review
- The Human Leukocyte Antigen (HLA)-B27 PeptidomeMolecular & cellular proteomics : MCP · 2017Article
- Human Leukocyte Antigen (HLA) B27 Allotype-Specific Binding and Candidate Arthritogenic Peptides Revealed through Heuristic Clustering of Data-independent Acquisition Mass Spectrometry (DIA-MS) Data.Molecular & cellular proteomics : MCP · 2016Article
- Structural Basis for Antigenic Peptide Recognition and Processing by Endoplasmic Reticulum (ER) Aminopeptidase 2.The Journal of biological chemistry · 2015Article
- Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A*29:02 Antigen.Molecular & cellular proteomics : MCP · 2015Article
- Revisiting MHC genes in spondyloarthritis.Current rheumatology reports · 2015Review
- Association of PTPN22 polymorphsims and ankylosing spondylitis susceptibility.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides identified only in AS-associated or high thermostability subtypes with identical A and B pockets were longer and had bulkier and more diverse C-terminal residues than those found only among non-AS-associated/lower-thermostability subtypes. Peptides sequenced from all AS-associated subtypes and not from non-AS-associated ones, thus strictly correlating with disease, were very rare. Residue 116 was critical in determining peptide binding, thermodynamic properties, and folding, thus emerging as a key feature that unified HLA-B27 biology. HLA-B27 ligands were better suited to TAP transport than their N-terminal precursors, and AS-associated subtype ligands were better than those from non-AS-associated subtypes, suggesting a particular capacity of AS-associated subtypes to bind epitopes directly produced in the cytosol. Peptides identified only from AS-associated/high-thermostability subtypes showed a higher frequency of ERAP1-resistant N-terminal residues than ligands found only in non-AS-associated/low-thermostability subtypes, reflecting a more pronounced effect of ERAP1 on the former group. Our results reveal the basis for the relationship between peptide specificity and other features of HLA-B27, provide a unified view of HLA-B27 biology and pathogenicity, and suggest a larger influence of ERAP1 polymorphism on AS-associated than non-AS-associated subtypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.