A double mutation of MBP_83–99 peptide induces IL-4 responses and antagonizes IFN-γ responses

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• 作者：Maria Katsara ; Elizabeth Yuriev ; Paul A. Ramsl ; George Deraos ; Theodore Tselios ; John Matsoukas ; Vasso Apostolopoulos
• 关键词：MS ; I-A^s ; MBP ; Vaccine ; Modeling ; Mutation
• 刊名：Journal of Neuroimmunology
• 出版年：2008
• 出版时间：30 August 2008
• 年：2008
• 卷：200
• 期：1-2
• 页码：77-89
• 全文大小：2295 K

文摘

A number of treatment options are available to multiple sclerosis patients, however this needs to be improved. Herein, we designed and synthesized a number of peptides by mutating principal TCR contact residues based on MBP_83–99 peptide epitope. Immunization of SJL/J mice with MBP_83–99 and mutant [A⁹¹]MBP_83–99, [E⁹¹]MBP_83–99, [F⁹¹]MBP_83–99, [Y⁹¹]MBP_83–99, and [R⁹¹, A⁹⁶]MBP_83–99 peptides, induced IFN-γ, and only [R⁹¹, A⁹⁶]MBP_83–99 mutant peptide was able to induce IL-4 secretion by T cells. T cells against the native MBP_83–99 peptide cross-reacted with all peptides except [Y⁹¹]MBP_83–99 and [R⁹¹,A⁹⁶]MBP_83–99. The double mutant [R⁹¹, A⁹⁶]MBP_83–99 was able to antagonize IFN-γ production in vitro by T cells against the native MBP_83–99 peptide. Antibodies generated to [R⁹¹, A⁹⁶]MBP_83–99 did not cross-react with whole MBP protein. Molecular modeling between peptide analogs and H2 I-A^s demonstrated novel interactions. The [R⁹¹, A⁹⁶]MBP_83–99 double mutant peptide analog is the most promising for further therapeutic studies.