Human anti-Ro autoantibodies bind peptides accessible to the surface of the native Ro autoantigen.
The relationship between fine specificity of linear epitopes and conformational determinants has been explored in a naturally arising human autoimmune response. In particular, the hypothesis tested is that the linear epitopes of the human Ro autoantigen are components of its conformational epitopes. Twenty groups among the 531 overlapping octapeptides 60 kDa Ro are variably bound by anti-Ro precipitin positive lupus sera whose reactivity was easily distinguished from sera of normal controls and of anti-Ro precipitin negative lupus patients. The specific activities of anti-peptide antibodies and of anti-native Ro autoantibodies are similarly increased after affinity enrichment using native human Ro as ligand. Moreover, affinity-enriched anti-native Ro autoantibodies bind virtually the same 20 groups of epitopes recognized by whole anti-Ro positive sera. Two peptides (residues 274-290 and 480-494) from the defined 60 kDa Ro octapeptide epitopes have been prepared and used as ligands for affinity purification of peptide specific autoantibodies. The binding of both whole IgG and affinity-enriched peptide specific autoantibodies is inhibited by native Ro autoantigen. Thus, none of the available data can be construed to support the existence of cryptic linear epitopes in this system. Indeed, the data are only consistent with the conclusion that all of the anti-Ro octapeptide autoantibodies are part of the population of anti-native Ro autoantibodies in this naturally arising autoimmune response.
Huang
S C
SC
Arthritis and Immunology Program, Oklahoma Medical Research Foundation.
Yu
H
H
Scofield
R H
RH
Harley
J B
JB
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000918:Antibody Specificity; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000737:chemistry / Q000276:immunology*; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D000939:Epitopes; D010446:Peptide Fragments; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human; C035356:SS-A antibodies