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A common autoepitope near the carboxyl terminus of the 60-kD Ro ribonucleoprotein: Sequence similarity with a viral protein

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Abstract

The Ro ribonucleoprotein is composed of hY RNA and a 60.7-kD peptide that is antigenic for autoantibodies produced by many patients with systemic lupus erythematosus or Sjögren's syndrome and mothers of newborns with complete congenital heart block. A major immunoreactive fragment (13 kD) of the 60-kD Ro is bound by 28 of 45 (62%) of the anti-Ro sera tested. Amino acid sequence analysis localizes this fragment to the carboxyl end of the 60-kD Ro peptide. All possible overlapping octapeptides of this 13-kD peptide of 60-kD Ro have been assessed for antigenicity. Sera that bind the 13-kD peptide fragment in immunoblot generally also bind the octapeptides of Ro spanning the sequence AIALREYRKKMDIPA (P<0.01). Inhibition studies with synthetic peptides and purified Ro have established specificity for reference serum antibody binding to an antigenic octapeptide, EYRKKMDI, from this region. The closely related sequence EYRKKLMD is found in the nucleocapsid protein of vesicular stomatitis virus and may portend an immunologic link to this or a related viral antigen. These results also demonstrate that despite fine specificity variation between human sera, there are recurring patterns of anti-Ro binding shared by some patients who have precipitating anti-Ro autoantibodies.

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References

  1. Harley JB, Gaither KK: Autoantibodies. Rheum Dis Clinics North Am. 14:43–56, 1988

    Google Scholar 

  2. Deutscher SL, Harley JB, Keene JD: Molecular analysis of the 60 kD human Ro ribonucleoprotein. Proc Natl Acad Sci 85:9479–9483, 1988

    Google Scholar 

  3. O'Brien CA, Harley JB: A subset of Y RNAs are associated with erythrocyte Ro ribonucleoproteins. EMBO J 9:3683–3689, 1990

    Google Scholar 

  4. Ben-Chetrit E, Chan EKL, Sullivan KF, Tan EM: A 52 kD protein is a novel component of the SS-A(Ro) antigenic particle. J Exp Med 1967:1560–1571, 1988

    Google Scholar 

  5. Rader MD, O'Brien CA, Lin Y, Harley JB, Reichlin M: The heterogeneity of the Ro antigen: Different molecular forms in lymphocytes and red blood cells. J Clin Invest 83:1293–1298, 1989

    Google Scholar 

  6. McCauliffe DP, Luk F, Lieu T-S, Sanz I, Hanke J, Newkirk MM, Bachinski LL, Itoh Y, Reichlin M, Sontheimer RD, Capra JD: Molecular cloning, expression and chromosome 19 localization of a human Ro/SS-A autoantigen. J Clin Invest 85:1379–1391, 1990

    Google Scholar 

  7. St. Clair EW, Pisetsky DS, Reich CF, Keene JD: Analysis of autoantibody binding to different regions of the human La antigen expressed in recombinant fusion proteins. J Immunol 141:4173–4180, 1988

    Google Scholar 

  8. Benjamin DC, Berzofsky JA, East IJ, Gurd FRN, Hannum C, Leach SJ, Margoliash E, Michael JG, Prager EW, Reichlin M, Sercarz EE, Smith-Gill SJ, Todd PE, Wilson AC: The antigenic structure of proteins, a reappraisal. Annu Rev Immunol 2:67–101, 1984

    Google Scholar 

  9. Geysen HM, Tainer JA, Rodda SJ, Mason TJ, Alexander H, Getzoff ED, Lerner RA: Chemistry of antibody binding to a protein. Science 235:1184–1190, 1987

    Google Scholar 

  10. Getzoff ED, Geysen HM, Rodda SJ, Alexander H, Trainer JA, Lerner RA: Mechanisms of antibody binding to a protein. Science 235:1191–1196, 1987

    Google Scholar 

  11. Guldner HH, Netter HJ, Szostecki C, Lokomek HJ, Will H: Epitope mapping with a recombinant human 68 kDa (U1) ribonucleoprotein antigen reveals heterogeneous profiles in human autoimmune sera. J Immunol 141:469–475, 1988

    Google Scholar 

  12. Harley JB, Reichlin M, Arnett FC, Alexander EL, Bias WB, Provost TT: Gene interaction at HLA-DQ enhances autoantibody production in primary Sjögren's syndrome. Science 232:1145–1147, 1986

    Google Scholar 

  13. Harley JB, Sestak AS, Willis LG, Fu SM, Hansen JA, Reichlin M: A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies and lymphopenia or renal disease. Arth Rheum 32:826–836, 1989

    Google Scholar 

  14. Fujisaku A, Frank MB, Neas B, Reichlin M, Harley JB: Evidence of gene complementation in man at HLA-DQ for anti-Ro/SSA autoantibodies. J Clin Invest 86:606–611, 1990

    Google Scholar 

  15. Frank MB, McArthur R, Harley JB, Fujisaku A: T cell receptor β gene polymorphisms define a subset of systemic lupus erythematosus patients with anti-Ro(SSA) autoantibodies. J Clin Invest 85:33–39, 1990

    Google Scholar 

  16. Yamagata H, Harley JB, Reichlin M: Molecular properties of the Ro/SSA antigen and enzyme-linked immunosorbent assay quantitation of antibody. J Clin Invest 74:625–633, 1984

    Google Scholar 

  17. Mamula MJ, Fox OF, Yamagata H, Harley JB: The Ro/SSA autoantigen as an immunogen: Some anti-Ro binds immunoglobulin G. J Exp Med 86:1889–1901, 1986

    Google Scholar 

  18. Houmard J, Drapeau GR: Staphylococcal protease: A proteolytic enzyme specific for glutamoyl bonds. Proc Natl Acad Sci USA 69:3506–3509, 1972

    Google Scholar 

  19. Matsudaira P: Sequence from picomole quantities of proteins electroblotted onto polyvinyladine difluoride membranes. J Chem 262:10035–10038, 1987

    Google Scholar 

  20. Geysen HM, Welden RH, Barteling SJ: Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci USA 81:3998–4002, 1984

    Google Scholar 

  21. Ben-Chetrit E, Gandy BJ, Tan EM, Sullivan KF: Isolation and characterization of a cDNA clone encoding the 60 kD component of the human SS-A/Ro ribonucleoprotein autoantigen. J Clin Invest 83:1284–1292, 1989

    Google Scholar 

  22. Merrifield RB: Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85:2149–2154, 1963

    Google Scholar 

  23. James JA, Dickey WD, Fujisaku A, O'Brien CA, Deutscher SL, Keene JD, Harley JB: Antigenicity of a recombinant Ro fusion protein. Arth Rheum 33:102–106, 1989

    Google Scholar 

  24. Devereaux J, Haeberli P, Marguess P: Sequence Analysis Software of the Genetics Computer Group. Madison, University of Wisconsin, 1987, pp 233–239

    Google Scholar 

  25. Jameson BA, Wolff H: The antigenic index: A novel algorithm for predicting antigenic determinants. CABIOS 4:181–187, 1988

    Google Scholar 

  26. Gallione CJ, Greene JR, Iverson LE, Rose JK: Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus N and NS proteins. J Virol 39:529–535, 1981

    Google Scholar 

  27. Scofield RH, Harley JB: Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus. Proc Natl Acad Sci USA 88:3343–3347, 1991

    Google Scholar 

  28. Van Vunakis H, Kaplan J, Lehrer H, Levine L: Immunogenicity of polylysine and polyornithine when complexed to phosphorolated bovine serum albumin. Immunochemistry 3:393–402, 1966

    Google Scholar 

  29. Appel JR, Pinilla C, Niman H, Houghton R: Elucidation of discontinuous linear determinants in peptide. J Immunol 144:976–983, 1990

    Google Scholar 

  30. Pisetsky DS, Grudier JP, Gilkeson, GS Gilkeson: A role for immunogenic DNA in the pathogenesis of systemic lupus erythematosus. Arth Rheum 33:153–159, 1990

    Google Scholar 

  31. Laver WG, Air GM, Webster RG, Smith-Gill SJ: Epitopes on protein antigens: Misconceptions and realities. Cell 61:553–556, 1990

    Google Scholar 

  32. Singh VK, Yamaki K, Donoso L, Shinohara T: Molecular mimicry: Yeast histone H3-induced experimental autoimmune uveitis. J Immunol 142:1512–1517, 1989

    Google Scholar 

  33. Cunningham MW, McCormack JM, Fenderson PG, Ho MK, Beachey EH, Dale JB: Human and murine antibodies cross-reactive with streptococcal M protein and myosin recognize the sequence GLN-LYS-SER-LYS-GLN in M protein. J Immunol 143:2677–2683, 1989

    Google Scholar 

  34. Yu DTY, Chou SY, Schaack T: Molecular mimicry and HLA-B27 related arthritis. Ann Intern Med 111:581–591, 1989

    Google Scholar 

  35. Gaither KK, Fox OF, Yamagata H, Manula M, Reichlin M, Harley JB: Implications of anti-Ro/SSA autoantibody in normal sera for autoimmunity. J Clin Invest 79:841–846, 1987

    Google Scholar 

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Scofield, R.H., Dickey, W.D., Jackson, K.W. et al. A common autoepitope near the carboxyl terminus of the 60-kD Ro ribonucleoprotein: Sequence similarity with a viral protein. J Clin Immunol 11, 378–388 (1991). https://doi.org/10.1007/BF00918804

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