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The Evolutionarily Conserved Ribosomal Protein L23 and the Cationic Urease β-Subunit of Yersinia enterocolitica O:3 Belong to the Immunodominant Antigens in Yersinia-Triggered Reactive Arthritis: Implications for Autoimmunity

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Abstract

Background

Reactive arthritis (ReA) is a T cell mediated inflammatory process. The immune response is primarily directed against a triggering organism, although autoimmunity has been invoked in long-lasting, antibiotic-resistant disease. Although a variety of different species are known to trigger Reactive arthritis, the clinical manifestations are strikingly similar as well as closely associated to the HLA-B27 (70%).

Materials and Methods

Various antigenic fractions and single antigens of Yersinia enterocolitica were prepared, and their immunological activity was assessed by proliferation of synovial fluid mononuclear cells from 10 Reactive arthritis patients. The gene encoding one hitherto unknown antigen has been sequenced. Nonapeptides deduced from sequences of the target antigens were tested in an assembly assay.

Results

Two immunodominant proteins of Yersinia enterocolitica were found, one being the urease β-subunit and the other the 50 S ribosomal protein L23. The latter has been sequenced and belongs to the evolutionarily conserved ribosomal proteins with homology to procaryotes and eucaryotes. One nonapeptide derived from the urease β-subunit was identified as a possible epitope for HLA-B27-restricted cytotoxic T cells by its high affinity. This epitope is also highly conserved.

Conclusion

Sharing of conserved immunodominant proteins between different disease triggering microorganisms could provide an explanation of the shared clinical picture in Reactive arthritis. Moreover, autoimmunity in Reactive arthritis might be mediated by antigen mimicry between evolutionarily conserved epitopes of ribosomal proteins and their host analogs.

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Acknowledgments

We would like to thank Emile Schiltz for performing the N-terminal sequencing of the L23 protein.

This study was supported by the Eberhard Bode-Stifung.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Andreas K. H. Mertz, Jürgen Braun, Heiner Appel, Armin Distler & Joachim Sieper

  2. Deutsches Rheumaforschungszentrum, Berlin, Germany

    Angelika Daser, Peihua Wu & Joachim Sieper

  3. Centre for Biotechnology, University of Turku, Turku, Finland

    Mikael Skurnik

  4. Naturwissenschaftliches und Medizinisches Institut, University of Tübingen, Reutlingen, Germany

    Karl-Heinz Wiesmüller

  5. Institute of Medical Microbiology, University of Frieburg, Frieburg, Germany

    Steven Batsford

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Mertz, A.K.H., Daser, A., Skurnik, M. et al. The Evolutionarily Conserved Ribosomal Protein L23 and the Cationic Urease β-Subunit of Yersinia enterocolitica O:3 Belong to the Immunodominant Antigens in Yersinia-Triggered Reactive Arthritis: Implications for Autoimmunity. Mol Med 1, 44–55 (1994). https://doi.org/10.1007/BF03403530

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