Correlation between chlamydial infection and autoimmune response: molecular mimicry between RNA polymerase major sigma subunit from Chlamydia trachomatis and human L7.
L7 is one of the ribosomal proteins frequently targeted by autoantibodies in rheumatic autoimmune diseases. A computer search revealed a region within the immunodominant epitope of L7 (peptide II) that is highly homologous to amino acid sequence 264-286 of the RNA polymerase major sigma factor of the eubacterium Chlamydia trachomatis. Anti-L7 autoantibodies affinity purified from the immunodominant epitope were able to recognize this sequence as they reacted with purified recombinant sigma factor. Immunofluorescence labeling experiments on C. trachomatis lysates revealed a punctate staining pattern of numerous spots when incubated with the affinity-purified anti-peptide II autoantibodies. Binding of autoantibodies to peptide II was inhibited by the homologous sigma peptide. This is the first demonstration of epitope mimicry between a human and a chlamydial protein on the level of B cells. Antibody screening revealed a significant correlation between the presence of anti-L7 autoantibodies and C. trachomatis infection in patients with systemic lupus erythematosus and mixed connective tissue disease. Our results suggest that molecular mimicry is involved in the initiation of anti-L7 autoantibody response and may represent a first glance into the immunopathology of Chlamydia with respect to systemic rheumatic diseases.
Hemmerich
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Department of Molecular Biology, Institute for Molecular Biotechnology, Jena, Germany. phemmer@imb-jena.de
Neu
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Macht
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Peter
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Krawinkel
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von Mikecz
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D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000097:blood; D000907:Antibodies, Bacterial / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D003429:Cross Reactions; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008947:Mixed Connective Tissue Disease / Q000276:immunology; D008969:Molecular Sequence Data; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D012808:Sigma Factor / Q000737:chemistry* / Q000276:immunology
D000974:Antibodies, Antinuclear; D000907:Antibodies, Bacterial; D001323:Autoantibodies; C053634:RPL7 protein, human; D012269:Ribosomal Proteins; D012808:Sigma Factor; C081775:RNA polymerase sigma 70; D012321:DNA-Directed RNA Polymerases