The DOI matches its Crossref record.
Cutting Edge: The Conversion of Arginine to Citrulline Allows for a High-Affinity Peptide Interaction with the Rheumatoid Arthritis-Associated HLA-DRB1*0401 MHC Class II Molecule
Abstract
Rheumatoid arthritis (RA) is genetically associated with MHC class II molecules that contain the shared epitope. These MHC molecules may participate in disease pathogenesis by selectively binding arthritogenic peptides for presentation to autoreactive CD4+ T cells. The nature of the arthritogenic Ag is not known, but recent work has identified posttranslationally modified proteins containing citrulline (deiminated arginine) as specific targets of the IgG Ab response in RA patients. To understand how citrulline might evoke an autoimmune reaction, we have studied T cell responses to citrulline-containing peptides in HLA-DRB1*0401 transgenic (DR4-IE tg) mice. In this study, we demonstrate that the conversion of arginine to citrulline at the peptide side-chain position interacting with the shared epitope significantly increases peptide-MHC affinity and leads to the activation CD4+ T cells in DR4-IE tg mice. These results reveal how DRB1 alleles with the shared epitope could initiate an autoimmune response to citrullinated self-Ags in RA patients.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Immunopathogenesis of Rheumatoid Arthritis
Firestein, G. S., & McInnes, I. B. (2017) · Immunity · doi:10.1016/j.immuni.2017.02.006 · Cited by 1,301
Scally, S. W., Petersen, J., Law, S. C., Dudek, N. L., Nel, H. J., Loh, K. L., Wijeyewickrema, L. C., Eckle, S. B. G., van Heemst, J., Pike, R. N., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20131241 · Cited by 429
Role of α-Synuclein in Inducing Innate and Adaptive Immunity in Parkinson Disease
Allen Reish, H. E., & Standaert, D. G. (2015) · Journal of Parkinson’s Disease · doi:10.3233/jpd-140491 · Cited by 244
Mechanisms involved in triggering rheumatoid arthritis
Catrina, A. I., Joshua, V., Klareskog, L., & Malmström, V. (2016) · Immunological Reviews · doi:10.1111/imr.12379 · Cited by 160
Vimentin as antigenic target in autoimmunity: A comprehensive review
Musaelyan, A., Lapin, S., Nazarov, V., Tkachenko, O., Gilburd, B., Mazing, A., Mikhailova, L., & Shoenfeld, Y. (2018) · Autoimmunity Reviews · doi:10.1016/j.autrev.2018.04.004 · Cited by 111
HLA-DR4 in Families With Autism
Lee, L.-C., Zachary, A. A., Leffell, M. S., Newschaffer, C. J., Matteson, K. J., Tyler, J. D., & Zimmerman, A. W. (2006) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2006.06.006 · Cited by 106
Post-translational modifications such as citrullination are excellent targets for cancer therapy
Brentville, V. A., Vankemmelbeke, M., Metheringham, R. L., & Durrant, L. G. (2020) · Seminars in Immunology · doi:10.1016/j.smim.2020.101393 · Cited by 53
Recent advances in understanding type 1 diabetes
Christoffersson, G., Rodriguez-Calvo, T., & von Herrath, M. (2016) · F1000Research · doi:10.12688/f1000research.7356.1 · Cited by 32
Ge, C., Weisse, S., Xu, B., Dobritzsch, D., Viljanen, J., Kihlberg, J., Do, N.-N., Schneider, N., Lanig, H., Holmdahl, R., et al. (2022) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2021-220500 · Cited by 26
Kelly, J. J., Bloodworth, N., Shao, Q., Shabanowitz, J., Hunt, D., Meiler, J., & Pires, M. M. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00312 · Cited by 15
Antigen presentation of post‐translationally modified peptides in major histocompatibility complexes
de Wit, A. S., Bianchi, F., & van den Bogaart, G. (2025) · Immunology & Cell Biology · doi:10.1111/imcb.12839 · Cited by 12
Metadata
- Authors
- Hill, J. A., Southwood, S., Sette, A., Jevnikar, A. M., Bell, D. A., & Cairns, E.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-07
- Volume
- 171
- Issue
- 2
- Pages
- 538-541
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2164744416
- Cited by
- 713
- References
- 0
- FWCI
- 23.96
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
