The evolutionarily conserved ribosomal protein L23 and the cationic urease beta-subunit of Yersinia enterocolitica O:3 belong to the immunodominant antigens in Yersinia-triggered reactive arthritis: implications for autoimmunity.
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%).


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 beta-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 beta-subunit was identified as a possible epitope for HLA-B27-restricted cytotoxic T cells by its high affinity. This epitope is also highly conserved.


CONCLUSIONS
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.
Mertz
A K
AK
Medizinische Klinik und Poliklinik, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
Daser
A
A
Skurnik
M
M
Wiesmüller
K H
KH
Braun
J
J
Appel
H
H
Batsford
S
S
Wu
P
P
Distler
A
A
Sieper
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000302:isolation & purification; D016918:Arthritis, Reactive / Q000276:immunology / Q000382:microbiology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D017124:Conserved Sequence; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D005260:Female; D015796:HLA-B27 Antigen / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D000091402:Prohibitins; D012269:Ribosomal Proteins / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014510:Urease / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015009:Yersinia Infections / Q000276:immunology; D015008:Yersinia enterocolitica / Q000276:immunology*
D000942:Antigens, Bacterial; D029968:Escherichia coli Proteins; D015796:HLA-B27 Antigen; D016056:Immunodominant Epitopes; C000717331:PHB2 protein, human; D010446:Peptide Fragments; D000091402:Prohibitins; D012269:Ribosomal Proteins; C043816:ribosomal protein L23, E coli; D014510:Urease