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 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 nonoverlapping 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 crossreact 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.
von Mikecz
A H
AH
Lehrstuhl für Immunologie, Fakultät für Biologie, Universität Konstanz, Freiburg, Germany.
Hemmerich
P H
PH
Peter
H H
HH
Krawinkel
U
U
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003429:Cross Reactions; D004023:Dictyostelium / Q000276:immunology; D018604:Epitope Mapping; D006801:Humans; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000276:immunology; D011994:Recombinant Proteins; D012269:Ribosomal Proteins / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D001324:Autoantigens; D016601:RNA-Binding Proteins; C053634:RPL7 protein, human; D011994:Recombinant Proteins; D012269:Ribosomal Proteins