查看文章

Mutations of peptides to generate altered peptide ligands, capable of switching immune responses from T helper 1 (Th1) to T helper 2 (Th2), are promising candidates for the immunotherapy of autoimmune diseases such as multiple sclerosis (MS). We synthesized two mutant peptides from myelin basic protein 87–99 (MBP_87–99), an immunodominant peptide epitope identified in MS. Mutations of residues K⁹¹ and P⁹⁶, known to be critical T‐cell receptor (TCR) contact sites, resulted in the mutant peptides [R⁹¹, A⁹⁶]MBP_87–99 and [A⁹¹, A⁹⁶]MBP_87–99. Immunization of mice with these altered peptide ligands emulsified in complete Freund’s adjuvant induced both interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) responses compared with only IFN‐γ responses induced to the native MBP_87–99 peptide. It was of interest that [R⁹¹, A⁹⁶]MBP_87–99 conjugated to reduced mannan induced 70% less IFN‐γ compared with …