Autoantigenic epitopes on eukaryotic L7
Ribosomal protein L7 has been established recently as a novel autoantigen representing a frequent target for autoantibodies from patients with systemic autoimmune diseases. Up to 75% of systemic lupus erythematosus (SLE) patients and 50% of mixed connective tissue disease (MCTD) and progressive systemic sclerosis (PSS) patients produce antibodies against in vitro translated L7 and form immunoprecipitable complexes. In this study the B cell response to protein L7 was investigated with respect to the immunogenic determinants recognized by autoantibodies. Eighteen truncated fragments of protein L7 were generated as recombinant fusions with glutathione‐S‐transferase and examined by immunoblotting for their reactivity with sera from patients suffering from systemic rheumatic diseases. Anti‐L7 antibodies target three major non‐overlapping autoepitopes. Two epitopes reside in the highly conserved C‐terminal part of the protein, whereas the N‐terminal autoepitope is not conserved during evolution. The N‐terminal epitope comprises 24 amino acid residues. Ten amino acid resides of this epitope are shared with the BZIP‐like RNA binding domain of protein L7. Autoantibodies recognizing this epitope cross‐react with the corresponding region of a L7 homologue, namely ribosomal protein L7 (RPL7) from Dictyostelium discoideum. This indicates that amino acid residues 14VPE…KKR22, which are conserved between humans and fungi, contribute essentially to the formation of autoantibody‐autoantigen complexes.