Identification of a human-specific epitope in a conserved region of the La/SS-B autoantigen.
Human anti-La/SS-B autoantibodies are known to react with highly conserved epitopes suggested to be functional or active sites on the La/SS-B polypeptide. This study was designed to determine whether the autoantibodies also react with poorly conserved regions of La/SS-B as predicted by an antigen-driven autoimmune response. Binding of human autoantibodies to purified human, mouse, and bovine recombinant fragments representing immunodominant regions of the La/SS-B polypeptide was compared using Western blotting and ELISA. A cross-reactive epitope was located in the highly conserved NH2-terminal region of La/SS-B. Significantly, human-specific epitopes were identified in both the conserved RNA-recognition motif and a poorly conserved COOH-terminal fragment, providing direct evidence for an autoantigen-driven response. The lack of autoantibody cross-reactivity with a conserved domain of mouse and bovine La/SS-B implies that a small number of residues in human autoepitopes may be critical for autoimmunogenicity.
Weng
Y M
YM
Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, South Australia.
McNeilage
J
J
Topfer
F
F
McCluskey
J
J
Gordon
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002417:Cattle; D017124:Conserved Sequence; D000939:Epitopes / Q000032:analysis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000097585:SS-B Antigen
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen