Epitope mapping with a recombinant human 68-kDa (U1) ribonucleoprotein antigen reveals heterogeneous autoantibody profiles in human autoimmune sera.
Several cDNA fragments encoding parts of the (U1)RNP specific 68-kDa autoantigen were expressed in Escherichia coli and the fusion proteins were used as substrate for localization of the autoreactive epitopes. We have identified a region of approximately 30 amino acids reacting with more than 90% (16 of 17) of all human anti-p68 sera tested, regions which carry only a few and a region with no autoepitopes. Comparative analysis of epitopes recognized on partially degraded fusion proteins indicated that the anti-p68 autoimmune response is polyclonal. It involves generation of antibodies to several epitopes including one in a region with retroviral gag protein homology speculated to play a role in the initiation of the autoimmune response. Each of the 17 sera tested contained a different set of autoantibody specificities. These data are not consistent with random mutation as a sole mechanism of anti-p68 autoantibody induction and argue for an Ag-driven autoimmune response.
Guldner
H H
HH
Max Planck Institut für Biochemie, Martinsried, Federal Republic of Germany.
Netter
H J
HJ
Szostecki
C
C
Lakomek
H J
HJ
Will
H
H
D000974:Antibodies, Antinuclear / Q000235:genetics*; D001324:Autoantigens / Q000235:genetics; D004268:DNA-Binding Proteins; D000939:Epitopes / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008947:Mixed Connective Tissue Disease / Q000235:genetics / Q000276:immunology*; D008970:Molecular Weight; D010449:Peptide Mapping; D012342:RNA, Small Nuclear / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology*; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004268:DNA-Binding Proteins; D000939:Epitopes; D012342:RNA, Small Nuclear; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins