Molecular structure of the La and Ro autoantigens and their use in autoimmune diagnostics

Abstract

Recombinant autoantigens of the La and Ro specificities have been produced and analyzed using immunological and genetic techniques. Human La cDNA and genomic clones were isolated that encode a protein of 46.7 kDa (408 amino acids). An active La gene consisting of 11 exons was localized on chromosome 2 and has an upstream transcriptional regulatory region resembling ‘housekeeping’ genes as well as elements homologous to the H-ras gene promoter which is presumably a ‘regulated’ gene. A long stretch of alpha helix is predicted in the middle of the La molecule and this region contains an immunodominant epitope. Human Ro protein is encoded by a 1.7 kb mRNA and is 60.6 kDa (538 amino acids) in size. A variety of cDNA clones was isolated and characterized, including those from liver, endothelium, brain and placenta. Long regions of predicted alpha helix also reside in the Ro protein but no sequence similarities to La protein have been found. A possible zinc finger motif that is characterestic of other known nucleic acid binding proteins resides near the middle of the Ro protein. Both the La and Ro proteins contain an extended RNA recognition motif about a region of 80 amino acids but they are less similar in this respect than the known snRNA-binding proteins [1].