The PPGMRPP repetitive epitope of the Sm autoantigen: Antigenic specificity induced by conformational changes. Application of the Sequential Oligopeptide Carriers (SOCs) |
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Authors: | Constantinos Sakarellos Vassilios Tsikaris Eugenia Panou-Pomonis Charalampos Alexopoulos Maria Sakarellos-Daitsiotis Constantinos Petrovas Panayiotis G Vlachoyiannopoulos and Haralampos M Moutsopoulos |
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Institution: | (1) Department of Chemistry, University of Ioannina, P.O. Box 1186, 45110 Ioannina, Greece;(2) Department of Pathophysiology, Medical School, National, University of Athens, 75 Mikras Asias, 11527 Athens, Greece |
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Abstract: | The PPGMRPP sequence, found in several copies in the Sm and U1RNPautoantigens, is the main target of anti-Sm and anti-U1RNP antibodies insystemic lupus erythematosus (SLE) and mixed connective tissue disease(MCTD) patient's sera. It is also recognized, to a lower extent, byanti-Ro/SSA and anti-La/SSB specificities. The PPGMRPP-NH2peptide amide and the PPGMRPP peptide, which is bound to a pentamericsequential oligopeptide carrier (SOC5), were examined by1H-NMR spectroscopy and ELISA assays, using sera from patientswith autoimmune rheumatic diseases. Among the three main conformers foundfor 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 theArg-guanidinium and the carboxylate group in the amide andSOC5-bound forms of the peptide. Immunoassays using sera fromvarious specificities showed an enhanced anti-Sm and anti-U1RNP recognitionof PPGMRPP-NH2 and(PPGMRPP)5-SOC5, and lowering of the anti-Ro/SSAand anti-La/SSB reactivity. The presence of multiple conformers of freePPGMRPP may explain the unexpected cross-reactivity to the anti-Ro/Lapositive sera, while the prevalence of the extended conformation inPPGMRPP-NH2 and (PPGMRPP)5-SOC5is mainly responsible for the enhanced recognition from the anti-Sm andanti-U1RNP autoantibodies. It is concluded that the antigenic specificity ofPPGMRPP-NH2 and (PPGMRPP)5-SOC5 ismainly induced by conformational changes resulting from the conversion ofthe C-terminal carboxylate group to the amide form. |
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Keywords: | Antigenicity of the Sm epitope Carriers of antigenic peptides Peptide conformation Proline-rich Sm epitope Sm autoantigen Systemic lupus erythematosus |
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