Epitopes described in "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."

Reference
Article Authors:Jonathan A Hill; Scott Southwood; Alessandro Sette; Anthony M Jevnikar; David A Bell; Ewa Cairns
Article Title: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.
Reference Detail
Reference ID:1014777
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.
Date:2003
Reference Type:Literature
PubMed ID:12847215
Journal:J Immunol
Journal Volume:171
Article Pages:538-41
Journal ISSN:0022-1767
Article Chemical List:HLA-DR Antigens;HLA-DR4 Antigen;HLA-DRB1 Chains;HLA-DRB1*04:01 antigen;Peptide Fragments;Vimentin;Citrulline;Arginine
Article MeSH List:Alleles; Animals; Arginine(metabolism); Arthritis, Experimental(genetics; immunology); Arthritis, Rheumatoid(genetics; immunology); Cells, Cultured; Citrulline(metabolism); HLA-DR Antigens(genetics; metabolism); HLA-DR4 Antigen(genetics; metabolism); HLA-DRB1 Chains; Humans; Lymphocyte Activation(genetics; immunology); Mice; Mice, Transgenic; Peptide Fragments(immunology; metabolism); Protein Binding(genetics; immunology); Protein Processing, Post-Translational(genetics; immunology); T-Lymphocytes(immunology); Vimentin(metabolism)
Curation Last Updated:2014-07-16 22:07:52