J. Malcolm
C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance
Malcolm, J.; Nyirenda, M. H.; Brown, J. L.; Adrados-Planell, A.; Campbell, L.; Butcher, J. P.; Glass, D. G.; Piela, K.; Goodyear, C. S.; Wright, A. J.; McInnes, I. B.; Millington, O. R.; Culshaw, S.
Authors
M. H. Nyirenda
J. L. Brown
A. Adrados-Planell
L. Campbell
J. P. Butcher
D. G. Glass
K. Piela
C. S. Goodyear
AMANDA WRIGHT Amanda.Wright@nottingham.ac.uk
Professor of Optics
I. B. McInnes
O. R. Millington
S. Culshaw
Abstract
In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity.
Citation
Malcolm, J., Nyirenda, M. H., Brown, J. L., Adrados-Planell, A., Campbell, L., Butcher, J. P., …Culshaw, S. (2023). C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance. Journal of Autoimmunity, 135, Article 102994. https://doi.org/10.1016/j.jaut.2023.102994
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 5, 2023 |
Online Publication Date | Jan 25, 2023 |
Publication Date | Feb 1, 2023 |
Deposit Date | Apr 18, 2023 |
Publicly Available Date | Apr 18, 2023 |
Journal | Journal of Autoimmunity |
Print ISSN | 0896-8411 |
Electronic ISSN | 1095-9157 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 135 |
Article Number | 102994 |
DOI | https://doi.org/10.1016/j.jaut.2023.102994 |
Keywords | Immunology; Immunology and Allergy |
Public URL | https://nottingham-repository.worktribe.com/output/16789928 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S0896841123000033?via%3Dihub |
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C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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