title: Immunization with an immunodominant self-peptide derived from glucose-6-phosphate isomerase induces arthritis in DBA/1 mice.
abstract: BACKGROUND
  T-helper (Th) lymphocytes are critically required for the pathogenesis of glucose-6-phosphate isomerase (G6PI)-induced arthritis, but neither the G6PI epitopes recognized by arthritogenic T cells nor their pathogenic effector functions have been fully elucidated to date. We aimed at identifying arthritogenic G6PI peptides.
  
  
  METHODS
  We used a library of overlapping peptides spanning the entire G6PI sequence to identify the epitopes recognized by G6PI-specific Th cells. Immunodominant peptides were then used to immunize mice. Arthritis development was evaluated clinically and histologically. The humoral and cellular immune responses upon peptide immunization were analyzed by ELISA and multiparameter flow cytometry, respectively.
  
  
  RESULTS
  We identified six immunodominant T-cell epitopes in DBA/1 mice, of which three are arthritogenic. One of these peptides (G6PI469-483) is identical in man and mice. Immunization with this peptide induces arthritis, which is less severe and of shorter duration than arthritis induced by immunization with full-length G6PI. Upon immunization with either G6PI or peptide, the antigen-specific Th cells produce IL-17, RANKL, IFNgamma and TNFalpha.
  
  
  CONCLUSIONS
  We identified immunodominant and arthritogenic epitopes of G6PI. Not all immunodominant peptides are arthritogenic. This is the first description of arthritis induced by immunization with a self-peptide in mice.
authors.affiliation: Universitätsklinikum Jena, Institut für Immunologie, Leutragraben 3, Jena, Germany. lisa.Bruns@mti.uni-jena.de
authors.forename: Lisa
authors.initials: L
authors.lastname: Bruns
authors.forename: Oliver
authors.initials: O
authors.lastname: Frey
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.forename: Christiane
authors.initials: C
authors.lastname: Landgraf
authors.forename: Rudolf
authors.initials: R
authors.lastname: Volkmer
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D005956:Glucose-6-Phosphate Isomerase