The Evolutionarily Conserved Ribosomal Protein L23 and the Cationic

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 /3-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 /3-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. Address correspondence and reprint requests to: Dr. Andreas Mertz, Medizinische Klinik und Poliklinik, Universitatsklinikum Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. Copyright © 1994, Molecular Medicine 44 A. K. H. Mertz et al.: Conserved Yersinia Antigens in Reactive Arthritis