Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system.

摘要: Breakdown in immunological self tolerance, leading to autoimmune diseases such as multiple sclerosis, might arise from immune recognition of proteins that have undergone heightened posttranslational modification under pathophysiological conditions. A particular interest is the deimination Arg citrulline, catalyzed by peptidylarginyl deiminase (PAD) enzymes. As a CD4+ T cell-driven model we used experimental encephalomyelitis (EAE) induced with immunodominant 35–55 peptide myelin oligodendrocyte glycoprotein (pMOG) C57BL/6 mice test whether citrullination cell epitope can contribute disease etiopathology. Immunization an altered ligand (APL) pMOG Arg→citrulline conversion at TCR contact (residue 41) led activation two populations APL-responsive cells either did, or did not cross-react native peptide. This APL could induce EAE. However, this reflected cross-reacted epitope, because prior tolerization these using prevented APL-induced Using passive transfer model, found responded specifically citrullinated form were neither necessary, nor sufficient initiate EAE lesion. Nevertheless, provoke exacerbation pathology if transferred into ongoing The PAD2 and PAD4 enzymes markedly upregulated inflamed CNS. Therefore, once inflammation established, target autoantigens allow expanded repertoire CNS pathology.