C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance

• DOI: 10.1016/j.jaut.2023.102994
• Publication Date: 2023-01-25T19:23:40Z
• Authors: J. Malcolm; M.H. Nyirenda; J.L. Brown; A. Adrados-Planell; L. Campbell; J.P. Butcher; D.G. Glass; K. Piela; C.S. Goodyear; A.J. Wright; I.B. McInnes; O.R. Millington; S. Culshaw
• Keywords: Citrullination; Alloimmunity; Peripheral tolerance

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable non-endogenous C-terminal citrullination potential to generate citrullinated autoantigens. Here we document how ovalbumin peptide323-339 alters interaction between antigen-presenting cells and OTII T induce functional changes in responding cells. These data reveal that sufficient peripheral vivo lower threshold for activation. Finally, demonstrate a role IL-2/STAT5/CD25 signalling axis tolerance. Together, our identify tractable mechanism targetable pathways arthritis provide new conceptual insight into origins autoimmunity.