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Open Access Research article

Immunization with an immunodominant self-peptide derived from glucose-6-phosphate isomerase induces arthritis in DBA/1 mice

Lisa Bruns1, Oliver Frey1, Lars Morawietz2, Christiane Landgraf3, Rudolf Volkmer3 and Thomas Kamradt1*

Author Affiliations

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

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Arthritis Research & Therapy 2009, 11:R117  doi:10.1186/ar2777

Published: 29 July 2009

Abstract

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.