Effect of amino acid substitutions within the region 62-76 of I-A beta b on binding with and antigen presentation of Torpedo acetylcholine receptor alpha-chain peptide 146-162.

摘要: Previous study has shown that reduced T cell response to peptide alpha 146-162 of Torpedo californica acetylcholine receptor (tAChR) in B6.C-H-2bm12 (bm12) mice, a mutant C57BL/6 (B6) correlated with its nonsusceptiblity experimental autoimmune myasthenia gravis. There are three amino acid differences between the I-A beta b two strains (positions 67, 70, and 71). We synthesized peptides b62-76 (peptide b6), bm1262-76 bm), additional peptides, b6(67F), b6(70Q), b6(71K), determined their ability bind dissociation constants (Kd) binding. Peptide bound significantly higher affinity b6 than bm or suggesting lower I-Abm12 is factor this by bm12 cells. This was confirmed measurement Kd values binding molecules B6 bm12. Furthermore, APC presented peptide, tAChR, poorly peptide-specific tAChR-specific The major effect caused change Thr-71 lysine However, also much less efficiently cells demonstrated these changes influence recognition peptide-MHC complex both recognizing tAChR under high H-2 restriction.