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Publication : Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species.

First Author  Keech CL Year  1996
Journal  Clin Exp Immunol Volume  104
Issue  2 Pages  255-63
PubMed ID  8625517 Mgi Jnum  J:32812
Mgi Id  MGI:80297 Doi  10.1046/j.1365-2249.1996.16726.x
Citation  Keech CL, et al. (1996) Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species. Clin Exp Immunol 104(2):255-63
abstractText  Anti-nuclear autoantibodies found in human autoimmune diseases frequently cross-react with homologous autoantigens in distant species, supporting the notion that autoantibodies target conserved functional domains. However, the 52-kD Ro(SS-A) protein is an exception, in that human autoantibodies are not known to recognize any equivalent antigen in the cells of rodents and other non-primate species. To understand this lack of cross-reactivity we have isolated cDNAs encoding the mouse 52-kD Ro molecule. The cDNA encoding mouse 52-kD Ro revealed an open reading frame of 470 amino acids, with 70% sequence identity to the human 52-kD Ro antigen. The putative leucine-zipper and zinc-finger motifs present in human Ro52 were conserved in the mouse protein. Recombinant mouse 52-kD Ro protein reacted with human autoantibodies by ELISA and immunoblot, but with approximately 10-fold lower reactivity than recombinant human 52-kD Ro protein under the same conditions. Detection of both human and mouse 52-kD Ro by immunoblot was dependent on antigen concentration which was limiting in the cell equivalents generally used in immunoblot assays. Differential chaotropic disruption of antibody binding suggested a lower avidity of human autoantibody binding to the mouse 52-kD Ro protein compared with the human antigen. Thus the poor reactivity of native mouse 52-kD Ro with human autoantibodies is associated with species divergence diffusely distributed throughout the primary structure of the 52-kD Ro molecule.
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