ArticlePloS one2017
Citrullination only infrequently impacts peptide binding to HLA class II MHC.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The trial behind it
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Who cites it
33 citing papers in PubMed.
- A specific amino acid motif ofProceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Review
- Distinct HLA Associations for Antibody Multireactivity With Citrulline-Containing Type II Collagen Epitopes Versus More Limited Antibody Reactivity With Citrulline-Containing IgG Epitopes in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Beyond natural amino acids: extending immunogenicity risk assessment to modified peptides through chemical feature encoding. A case study on citrullination.Frontiers in immunology · 2026Article
- The Role of Vimentin Peptide Citrullination in the Structure and Dynamics of HLA-DRB1 Rheumatoid Arthritis Risk-Associated Alleles.International journal of molecular sciences · 2024Article
- Crucial Parameters for Immunopeptidome Characterization: A Systematic Evaluation.International journal of molecular sciences · 2024Article
- The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population.RMD open · 2024Article
- Significance of Type II Collagen Posttranslational Modifications: From Autoantigenesis to Improved Diagnosis and Treatment of Rheumatoid Arthritis.International journal of molecular sciences · 2023Review
- How does citrullination contribute to RA autoantibody development?Nature reviews. Rheumatology · 2023Article
- Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis.Nature communications · 2023Article
- PAD2 immunization induces ACPA in wild-type and HLA-DR4 humanized mice.European journal of immunology · 2022Article
- Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor.Annals of the rheumatic diseases · 2022Article
- PAD4 Immunization Triggers Anti-Citrullinated Peptide Antibodies in Normal Mice: Analysis With Peptide Arrays.Frontiers in immunology · 2022Article
- How RA Associated HLA-DR Molecules Contribute to the Development of Antibodies to Citrullinated Proteins: The Hapten Carrier Model.Frontiers in immunology · 2022Review
- Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies.Cells · 2021Review
- Comparison of HLA ligand elution data and binding predictions reveals varying prediction performance for the multiple motifs recognized by HLA-DQ2.5.Immunology · 2021Article
- Article
- Anti-cyclic-citrullinated-protein-antibodies in psoriatic arthritis patients: how autoimmune dysregulation could affect clinical characteristics, retention rate of methotrexate monotherapy and first line biotechnological drug survival. A single center retrospective study.Therapeutic advances in chronic disease · 2021Article
- B Cells in Rheumatoid Arthritis：Pathogenic Mechanisms and Treatment Prospects.Frontiers in immunology · 2021Review
- Citrullinated Epitopes Identified on Tumour MHC Class II by Peptide Elution Stimulate Both Regulatory and Th1 Responses and Require Careful Selection for Optimal Anti-Tumour Responses.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1*01:01 and DRB1*04:01. The overall effect of citrullination on binding was found to be relatively minor, and only rarely associated with 3-fold increases or decreases in affinity. Previous studies have suggested that citrullination of MHC anchor residues, in particular P4, is associated with generation of novel RA-associated epitopes. However, analysis of the predicted MHC-binding cores of all peptides tested found that in modified peptides with increased binding affinity the citrullinated residue was predicted to occupy an anchor position in only a minority of cases. Finally, we also show that identification of citrullinated peptide binders could be facilitated by using the NetMHCIIpan 3.1 algorithm, representing citrullination as a wildcard. Our studies identify a total of 117 citrullinated peptides that bound RA-associated alleles with an affinity of 1000 nM or better.
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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.