Small Nuclear RNA-Associated Proteins are Immunologically Related as Revealed by Mapping of Autoimmune Reactive B-Cell Epitopes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-06, Vol.86 (12), p.4674-4678
• Main Authors: Habets, Winand J., Peter T. G. Sillekens, Hoet, Margot H., McAllister, George, Lerner, Michael R., Van Venrooij, Walther J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Antibodies; Autoantibodies; Autoimmunity (experimental aspects and models); B-Lymphocytes - immunology; Biological and medical sciences; Cell Nucleus - analysis; Cross Reactions; Enzyme linked immunosorbent assay; Epitopes; Epitopes - analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HeLa cells; HeLa Cells - analysis; Humans; Immunology; Molecular Sequence Data; Peptide Mapping; Proteins; Recombinant Proteins - immunology; Ribonucleoproteins - genetics; Ribonucleoproteins - immunology; Ribonucleoproteins, Small Nuclear; Small nuclear ribonucleoproteins; Systemic lupus erythematosus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.12.4674

Autoantibodies from a patient with systemic lupus erythematosus, which recognize U1 and U2 small nuclear ribonucleoprotein particles (snRNPs), were used to map B-cell autoepitopes on the U1 snRNP-specific A protein. This protein contains two regions that are highly similar to regions in the U2 snRNP-specific B′ ′protein. A site termed epitope 2 maps in one such region and was found to react with antibodies cross-reactive between A and B′ ′. A second site, epitope 1, is situated in a proline-rich region that shows no homology with B′ ′. This epitope can bind three different autoantibodies with distinct specificities. Epitope 1-affinity-purified antibodies from different patients react with either (i) the A protein exclusively; (ii) proteins A, B′/B, a synthetic peptide for part of the N polypeptide, and an unidentified protein with a molecular mass of 50 kDa; or (iii) proteins A, B′/B, C, and the N-derived peptide. Comparison of the primary structures of proteins B′/B, N, and C reveals multiple epitope 1-like sequences in all of them. The possibility that these repeating regions act as immunogens in patients with autoimmune diseases is discussed.