Molecular Basis for CD4+ T cell Recognition of Citrullinated Self-antigens in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is widely recognized as a T cell–mediated autoimmune disease, in which T cells play a central role by recognizing and targeting self-antigens, particularly those that have undergone post-translational modification through citrullination. In this thesis, we elucidate the structural basis of T cell recognition in response to citrullinated peptide antigens, namely citrullinated Tenascin. Through structural and comprehensive biochemical analyses, we demonstrate that citrullination plays a critically essential role in TCR recognition by directly determining the binding specificity of the TCR . Overall, our findings provide molecular insights of citrullination nmodulating TCR recognition in the context of RA.