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.
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References
Tam, E.M., Adv. Immunol., 33 (1982) 167.
Lerner, M.R. and Steitz, J.A., Proc. Natl. Acad. Sci. USA, 76 (1979) 5495.
Rockeach, L.A. and Hoch, S.O., Mol. Biol. Rep., 16 (1992) 165.
Bringmann, P. and Luhrmann, R., EMBO J., 5 (1986) 3509.
Billings, P.B. and Hosh, S.O., J. Biol. Chem., 259 (1984) 12850.
Pettersson, I., Wang, G., Smith, E.I., Wigzell, H., Hedfors, E., Horn, J. and Sharp, G.C., Arthritis Rheum., 29 (1986) 986.
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.
James, J.A., Gross, T., Scofield, R.H. and Harley, J.B., J. Exp. Med., 181 (1995) 453.
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.
Tsikaris, V., Sakarellos, C., Cung, M.T., Marraud, M. and Sakarellos-Daitsiotis, M., Biopolymers, 38 (1996) 291.
Tsikaris, V., Sakarellos, C., Sakarellos-Daitsiotis, M., Cung, M.T., Marraud, M., Vatzaki, E. and Tzartos, S., Int. J. Biol. Macromol., 19 (1996) 195.
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.
Merrifield, R.B., J. Am. Chem. Soc., 85 (1963) 2149
Kaiser, E., Colescott, R.L., Bossinger, P.D. and Cook, P.F., Anal. Biochem., 34 (1970) 595.
Blake, J. and Li, C.H., J. Am. Chem. Soc., 90 (1968) 5882.
Stewart, J.M. and Young, J.D. (Eds) Solid-Phase Peptide Synthesis. Pierce Chemical Co., Rockford, IL, U.S.A., 1984.
Ane, W.P., Bartholdi, E. and Ernst, R.R., J. Chem. Phys., 64 (1976) 2229.
Bax, A. and Davis, D.G., J. Magn. Reson., 65 (1985) 355.
Bodenhausen, G., Kogler, H. and Ernst, R.R., J. Magn. Reson., 58 (1984) 370.
Guialis, A., Dangli, A. and Sekeris, C.E., Mol. Cell Biochem., 76 (1987) 147.
Kurata, N. and Tan, E.M., Arthritis Rheum., 19 (1976) 574.
Tsikaris, V., Sakarellos-Daitsiotis, M., Theophanidis, N., Sakarellos, C., Cung, M.T. and Marraud, M., J. Chem. Soc., Perkin Trans. 2, (1991) 1353.
Tsikaris, V., Sakarellos-Daitsiotis, M., Panou-Pomonis, E., Detsikas, E., Sakarellos, C., Cung, M.T. and Marraud, M., Pept. Res., 5 (1992) 110.
Tsikaris, V., Sakarellos-Daitsiotis, M., Panou-Pomonis, E., Sakarellos, C. and Cung, M.T., J. Chem. Soc., Perkin Trans. 2, (1993) 1345.
Tsikaris, V., Sakarellos-Daitsiotis, M., Tzovaras, D., Sakarellos, C., Orlewski, P., Cung, M.T. and Marraud, M., Biopolymers, 38 (1996) 673.
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.
Orlewski, P., Tsikaris, V., Sakarellos-Daitsiotis M., Sakarellos, C., Soteriadou, K.P., Marraud, M., and Cung, M.T., Lett. Pept. Sci., 3 (1996) 317.
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Sakarellos, C., Tsikaris, V., Panou-Pomonis, E. et al. The PPGMRPP repetitive epitope of the Sm autoantigen: Antigenic specificity induced by conformational changes. Application of the Sequential Oligopeptide Carriers (SOCs). Lett Pept Sci 4, 447–454 (1997). https://doi.org/10.1007/BF02442915
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DOI: https://doi.org/10.1007/BF02442915