A Yersinia pseudotuberculosis protein which cross-reacts with HLA-B27.
The most-debated question in the investigation of the spondyloarthropathies has been whether there is molecular mimicry between host HLA-B27 antigens and the arthritis-causing pathogens. We have generated a monoclonal anti-HLA-B27 antibody in our laboratory and have used a radioimmunoassay to screen a panel of bacterial species. Two strains of Yersinia pseudotuberculosis were found to be highly reactive. The cross-reactive Yersinia component was identified by Western blot to be a 19,000 component. A preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis chromatography apparatus was constructed to isolate milligram quantities of this component. To verify that the component carried the HLA-B27-specific epitope, rabbits were hyperimmunized with the purified materials. Affinity-purified antibodies from one of the immunized rabbits indeed carried anti-HLA-B27 activity. Last, antibodies generated against synthetic peptides derived from the HLA-B27.1 amino acid sequence were tested against the Yersinia component. Positive reactivity was found with antibodies generated against a peptide spanning residues 69-83 of the HLA-B27.1 protein. Since this resides in the segment responsible for the allotypic specificity of the antigen, these experiments establish the presence of molecular mimicry to a high degree of confidence.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes; D006680:HLA Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen; D006801:Humans; D008970:Molecular Weight; D010455:Peptides / Q000276:immunology; D013045:Species Specificity; D015011:Yersinia pseudotuberculosis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D000939:Epitopes; D006680:HLA Antigens; D015796:HLA-B27 Antigen; D010455:Peptides