Identification of antigenic regions of the human 52kD Ro/SS-A protein recognized by patient sera

Patients with several different connective tissue diseases including Sjögren's syndrome and systemic lupus erythematosus produce autoantibodies reacting with a 52kD protein component of the Ro/SS-A antigen. Antibody recognition of recombinant Ro 52kD proteins encoded by both full-length and deletion clones was analysed by immunoblotting with patient sera. An antigenic region recognized by all anti-Ro 52kD positive sera was found in the middle part of the protein. By further mapping of residues 136-292 with overlapping clones, at lest two independent epitopes within the domain were detected. This part of the protein contains a leucine zipper motif and shows structural similarities with a predicted coiled-coil region involved in protein dimer formation. In addition, one fifth of the sera reacted weakly with another antigenic region located in the amino-terminal part of the protein containing two putative zinc fingers. These results demonstrate the presence of an immunodominant region but also heterogeneity in the human autoimmune response to the 52kD protein moiety of the Ro/SS-A antigen.