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Letters in Peptide Science

, Volume 4, Issue 4–6, pp 447–454 | Cite as

The PPGMRPP repetitive epitope of the Sm autoantigen: Antigenic specificity induced by conformational changes. Application of the Sequential Oligopeptide Carriers (SOCs)

  • Constantinos Sakarellos
  • Vassilios Tsikaris
  • Eugenia Panou-Pomonis
  • Charalampos Alexopoulos
  • Maria Sakarellos-Daitsiotis
  • Constantinos Petrovas
  • Panayiotis G. Vlachoyiannopoulos
  • Haralampos M. Moutsopoulos
Article

Summary

The PPGMRPP sequence, found in several copies in the Sm and U1RNP autoantigens, is the main target of anti-Sm and anti-U1RNP antibodies in systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) patient's sera. It is also recognized, to a lower extent, by anti-Ro/SSA and anti-La/SSB specificities. The PPGMRPP-NH2 peptide amide and the PPGMRPP peptide, which is bound to a pentameric sequential oligopeptide carrier (SOC5), were examined by1H-NMR spectroscopy and ELISA assays, using sera from patients with autimmune rheumatic diseases. Among the three main conformers found for the free PPGMRPP, the extended one was also identified for PPGMRPP-NH2 and (PPGMRPP)5-SOC5. This can be attributed to the absence of ionic interactions between the Arg-guanidinium and the carboxylate group in the amide and SOC5-bound forms of the peptide. Immunoassays using sera from various specificities showed an enhanced anti-Sm and anti-U1RNP recognition of PPGMRPP-NH2 and (PPGMRPP)5-SOC5, and lowering of the anti-Ro/SSA and anti-La/SSB reactivity. The presence of multiple conformers of free PPGMRPP may explain the unexpected cross-reactivity to the anti-Ro/La positive sera, while the prevalence of the extended conformation in PPGMRPP-NH2 and (PPGMRPP)5-SOC5 is mainly responsible for the enhanced recognition from the anti-Sm and anti-U1RNP autoantibodies. it is concluded that the antigenic specificity of PPGMRPP-NH2 and (PPGMRPP)5-SOC5 is mainly induced by conformational changes resulting from the conversion of the C-terminal carboxylate group to the amide form.

Keywords

Antigenicity of the Sm epitope Carriers of antigenic peptides Peptide conformation Proline-rich Sm epitope Sm autoantigen Systemic lupus erythematosus (SLE) 

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References

  1. 1.
    Tam, E.M., Adv. Immunol., 33 (1982) 167.CrossRefGoogle Scholar
  2. 2.
    Lerner, M.R. and Steitz, J.A., Proc. Natl. Acad. Sci. USA, 76 (1979) 5495.PubMedCrossRefGoogle Scholar
  3. 3.
    Rockeach, L.A. and Hoch, S.O., Mol. Biol. Rep., 16 (1992) 165.CrossRefGoogle Scholar
  4. 4.
    Bringmann, P. and Luhrmann, R., EMBO J., 5 (1986) 3509.PubMedGoogle Scholar
  5. 5.
    Billings, P.B. and Hosh, S.O., J. Biol. Chem., 259 (1984) 12850.PubMedGoogle Scholar
  6. 6.
    Pettersson, I., Wang, G., Smith, E.I., Wigzell, H., Hedfors, E., Horn, J. and Sharp, G.C., Arthritis Rheum., 29 (1986) 986.PubMedGoogle Scholar
  7. 7.
    Ohosone, Y., Mimori, I., Fujii, T., Akizuki, M., Matuoka, Y., Irimajiri, S., Hardin, J.A., Craft, J. and Homma, M., Arthritis Rheum., 35 (1992) 960.PubMedGoogle Scholar
  8. 8.
    James, J.A., Gross, T., Scofield, R.H. and Harley, J.B., J. Exp. Med., 181 (1995) 453.PubMedCrossRefGoogle Scholar
  9. 9.
    Tsikaris, V., Vlachoyiannopoulos, P.G., Panou-Pomonis, E., Marraud, M., Sakarellos, C., Moutsopoulos, H.M. and Sakarellos-Daitsiotis, M., Int. J. Pept. Protein Res., 48 (1996) 319.PubMedCrossRefGoogle Scholar
  10. 10.
    Tsikaris, V., Sakarellos, C., Cung, M.T., Marraud, M. and Sakarellos-Daitsiotis, M., Biopolymers, 38 (1996) 291.PubMedCrossRefGoogle Scholar
  11. 11.
    Tsikaris, V., Sakarellos, C., Sakarellos-Daitsiotis, M., Cung, M.T., Marraud, M., Vatzaki, E. and Tzartos, S., Int. J. Biol. Macromol., 19 (1996) 195.PubMedCrossRefGoogle Scholar
  12. 12.
    Tsikaris, V., Sakarellos, C., Sakarellos-Daitsiotis, M., Cung, M.T., Marraud, M., Konidou, G., Tzinia, A. and Soteriadou, K.P., Pept. Res., 9 (1996) 240.PubMedGoogle Scholar
  13. 13.
    Merrifield, R.B., J. Am. Chem. Soc., 85 (1963) 2149CrossRefGoogle Scholar
  14. 14.
    Kaiser, E., Colescott, R.L., Bossinger, P.D. and Cook, P.F., Anal. Biochem., 34 (1970) 595.PubMedCrossRefGoogle Scholar
  15. 15.
    Blake, J. and Li, C.H., J. Am. Chem. Soc., 90 (1968) 5882.PubMedCrossRefGoogle Scholar
  16. 16.
    Stewart, J.M. and Young, J.D. (Eds) Solid-Phase Peptide Synthesis. Pierce Chemical Co., Rockford, IL, U.S.A., 1984.Google Scholar
  17. 17.
    Ane, W.P., Bartholdi, E. and Ernst, R.R., J. Chem. Phys., 64 (1976) 2229.CrossRefGoogle Scholar
  18. 18.
    Bax, A. and Davis, D.G., J. Magn. Reson., 65 (1985) 355.Google Scholar
  19. 19.
    Bodenhausen, G., Kogler, H. and Ernst, R.R., J. Magn. Reson., 58 (1984) 370.Google Scholar
  20. 20.
    Guialis, A., Dangli, A. and Sekeris, C.E., Mol. Cell Biochem., 76 (1987) 147.PubMedCrossRefGoogle Scholar
  21. 21.
    Kurata, N. and Tan, E.M., Arthritis Rheum., 19 (1976) 574.PubMedGoogle Scholar
  22. 22.
    Tsikaris, V., Sakarellos-Daitsiotis, M., Theophanidis, N., Sakarellos, C., Cung, M.T. and Marraud, M., J. Chem. Soc., Perkin Trans. 2, (1991) 1353.Google Scholar
  23. 23.
    Tsikaris, V., Sakarellos-Daitsiotis, M., Panou-Pomonis, E., Detsikas, E., Sakarellos, C., Cung, M.T. and Marraud, M., Pept. Res., 5 (1992) 110.PubMedGoogle Scholar
  24. 24.
    Tsikaris, V., Sakarellos-Daitsiotis, M., Panou-Pomonis, E., Sakarellos, C. and Cung, M.T., J. Chem. Soc., Perkin Trans. 2, (1993) 1345.Google Scholar
  25. 25.
    Tsikaris, V., Sakarellos-Daitsiotis, M., Tzovaras, D., Sakarellos, C., Orlewski, P., Cung, M.T. and Marraud, M., Biopolymers, 38 (1996) 673.PubMedCrossRefGoogle Scholar
  26. 26.
    Sakarellos-Daitsiotis, M., Panou-Pomonis, E., Sakarellos, C., Cung, M.T., Marraud, M., Tzinia, A.K., Soteriadou, K.P. and Tsikaris, V., Lett. Pept. Sci., 3 (1996) 200.CrossRefGoogle Scholar
  27. 27.
    Orlewski, P., Tsikaris, V., Sakarellos-Daitsiotis M., Sakarellos, C., Soteriadou, K.P., Marraud, M., and Cung, M.T., Lett. Pept. Sci., 3 (1996) 317.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Constantinos Sakarellos
    • 1
  • Vassilios Tsikaris
    • 1
  • Eugenia Panou-Pomonis
    • 1
  • Charalampos Alexopoulos
    • 1
  • Maria Sakarellos-Daitsiotis
    • 1
  • Constantinos Petrovas
    • 2
  • Panayiotis G. Vlachoyiannopoulos
    • 2
  • Haralampos M. Moutsopoulos
    • 2
  1. 1.Department of ChemistryUniversity of IoanninaIoanninaGreece
  2. 2.Department of Pathophysiology, Medical SchoolNational University of AthensAthensGreece

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