A disease-related epitope of Torpedo acetylcholine receptor : residues involved in I-Ab binding, self-nonself discrimination, and TCR antagonism

摘要: Residues 146-162 of the Torpedo californica acetylcholine receptor alpha-subunit contain immunodominant T cell epitope for experimental autoimmune myasthenia gravis-susceptible C57BL/6 mice. To develop potential therapeutic peptides, a detailed analysis was undertaken. Truncated and substituted synthetic peptides were tested as stimulators clones immune lymph node cells. Critical residues spanned positions 151-159. Y151 V156 critical MHC binding. The results indicated general motif binding to I-Ab be an aromatic or hydrophobic residue (preferentially Y F) at position i followed by uncharged (i + 5). Lysine not tolerated 8). D152, K155, S157, I158 important contact residues. A peptide corresponding murine sequence, which differs from sequence 5 residues, bound but nonimmunogenic, consistent with assigned TCR These suggest that tolerance is responsible lack cross-reactivity receptor. Substituted inhibition clone responses antagonism. Although 157 158 inhibited most clones, no single could completely inhibit all primed findings indicate antagonist may useful in inhibiting complex Ag displaying epitope. Multiple antagonists used combination required maximum response.