Research article
Immunization with an immunodominant self-peptide derived from glucose-6-phosphate isomerase induces arthritis in DBA/1 mice
1 Universitätsklinikum Jena, Institut für Immunologie, Leutragraben 3, Jena 07740, Germany
2 Charité Universitätsmedizin Berlin, Institut für Pathologie, Charitéplatz 1, Berlin 10117, Germany
3 Charité Universitätsmedizin Berlin, Institut für Medizinische Immunologie, Charitéplatz 1, Berlin 10117, Germany
Arthritis Research & Therapy 2009, 11:R117 doi:10.1186/ar2777
Published: 29 July 2009Abstract
Introduction
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, IFNγ and TNFα.
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.
