Analysis of autoantibodies to recombinant La (SS-B) peptides in systemic lupus erythematosus and primary Sjogren's syndrome.
Autoantibodies to a polymerase III transcription factor, La (SS-B), are frequently detected in the serum of patients with Sjogren's syndrome and systemic lupus erythematosus. To define the humoral immune response to this protein, we analyzed the patterns of antibody recognition toward 13 recombinant La peptides by immunoblotting and determined the heterogeneity of antibodies reactive with the immunodominant epitopes. The smallest epitopes that were strongly antigenic and recognized by greater than 70% of sera tested (immunodominant) were encoded by the subclones BgX and XA located in the 5' and 3' halves of the La cDNA, respectively. Conformation of the immunodominant La peptides played a major role in antibody recognition. Although greater diversity in antibody binding to carboxyl-terminal La peptides was observed, the overall pattern of peptide recognition by anti-La antibodies was similar in different diseases. The antibody responses to the immunodominant peptides were strongly correlated (r = 0.68, P less than 0.001). One- and two-dimensional isoelectric focusing of affinity purified IgG anti-La peptide antibodies revealed restricted heterogeneity and oligoclonal bands (kappa light chains). These observations suggest that anti-La antibodies are induced and/or maintained by the self antigen and that their diversity is constrained either by mechanisms related to tolerance or by affinity maturation of the humoral immune response.
Hospital for Special Surgery, Cornell University Medical Center, New York, New York 10021.
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Bini
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Chu
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Okolo
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Elkon
D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000032:analysis; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology*; D012261:Ribonucleoproteins; D012859:Sjogren's Syndrome / Q000276:immunology*; D000097585:SS-B Antigen
D001323:Autoantibodies; D001324:Autoantigens; D004247:DNA; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen