Polyclonal human rheumatoid factors cross-reacting with histone H3: characterization of an idiotope on the H3 binding site.
The development of highly sensitive immunoassays has made the detection of the multireactivity of antibodies a relatively common phenomenon. Polyreactivity is frequent in human auto antibodies, especially in rheumatoid factors (RFs), but the structural basis and the significance of this phenomenon remain substantially unknown. Recently, we showed that the double reactivity of a human monoclonal RF with histones was probably due to two distinct binding sites. However, cross-reactivity seems more frequent among polyclonal RFs occurring during autoimmune diseases than with monoclonal RFs. We studied double-reactive (IgG and histone H3) polyclonal RFs in a patient suffering from primary Sjögren's syndrome. We showed by means of affinity chromatographies that H3 cross-reactive RFs were only a small subset of the total patient's RFs and that this subset was enriched in IgA class. Competitive inhibition experiments suggested the existence of two distinct binding sites for IgG and H3. These results were confirmed by showing the selective sensitivity to acid treatment of the histone binding site and by producing a murine antiidiotope monoclonal antibody BII 2.1 defining an idiotope on bireactive RF apparently linked to the H3 binding site. This idiotope was absent in a panel of monoclonal RF, one of them cross-reacting with histone H3. This report extends previous results concerning a monoclonal RF to the polyclonal RFs which occur during autoimmune diseases.
Laboratoire d'Immunopathologie, Clinique Médicale A, Hôpital Central CHU, Strasbourg, France.
T
T
Martin
A M
AM
Knapp
S
S
Muller
J L
JL
Pasquali
D000143:Acids; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D006657:Histones / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*
D000143:Acids; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D006657:Histones; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012217:Rheumatoid Factor