Monoclonal antibodies to the main immunogenic region of the nicotinic acetylcholine receptor bind to residues 61-76 of the alpha subunit.

The third-dimensional structure of the complex between an Fv antibody fragment and an analogue of the main immunogenic region of the acetylcholine receptor: A combined two-dimensional NMR, homology, and molecular modeling approach

“…The production and characteristics of the mAb have been described earlier. 3,4,7 Bacterial expression and sequencing of the scFv fragment of anti-AChR mAb198 have been reported elsewhere. 24 [G 70 , Nle 76 ]MIR was synthesized using standard solid-phase peptide chemistry on phenyl acetamido methyl (PAM) resin.…”

“…2 Previous investigations have shown that two thirds of the anti-AChR antibodies found in patients or in immunized rats are directed against a small region of the AChR sequence, named the "main immunogenic region" (MIR). 1,3,4 A major part of the MIR has been localized between residues 67-76 of the AChR ␣-subunit. The ␣67-76 sequence is W 67 -N 68 -P 69 -A 70 -D 71 -Y 72 -G 73 -G 74 -I 75 -K 76 in Torpedo electric organ AChR and W 67 -N 68 -P 69 -D 70 -D 71 -Y 72 -G 73 -G 74 -V 75 -K 76 in human muscle AChR, with one nonconservative (␣70) and one conservative (␣75) substitution.…”

“…The ␣67-76 sequence is W 67 -N 68 -P 69 -A 70 -D 71 -Y 72 -G 73 -G 74 -I 75 -K 76 in Torpedo electric organ AChR and W 67 -N 68 -P 69 -D 70 -D 71 -Y 72 -G 73 -G 74 -V 75 -K 76 in human muscle AChR, with one nonconservative (␣70) and one conservative (␣75) substitution. 3,4 Structural studies in solution revealed essential sequential and structural characteristics of different MIR peptide analogues. 5 Sequence alanine scanning revealed the important roles of residues N 68 , P 69 , and D 71 in the recognition process, since substitution of any one of these residues greatly impaired antibody binding.…”

Μελετη Της Βαρειας Μυασθενειας Και Του Υποδοχεα Της Ακετυλοχολινης Με Την Βοηθεια Μονοκλωνικων Αντισωματων

“…Ακολούθως η MIR του AChR των μυών θυλαστικών εντο πίσθηκε μεταξύ των αμινοξέων 6-85 και στην συνέχεια μεταξύ των 37-85 με την χρησιμοποίηση ανασυνδιασμένων βακτηριακών πρωτεϊνών σύντηξης οι οποίες περιείχαν τμήματα της α-υπομονά-/ ΘΕΩΡΗΤΙΚΟ ΜΕΡΟΣ δας (Barkas et al 1987a(Barkas et al , 1987b. Με την χρησιμοποίηση συνθετι κών πεπτιδίων που αντιστοιχούσαν στο μεγαλύτερο μέρος της αν θρώπινης α-υπομονάδας η MIR εντοπίσθηκε μεταξύ των αμινοξέων 63-80 (Tzartos et al 1988a), ενώ αντίστοιχα πειράματα με την αυπομονάδα του Torpedo την εντόπισαν ανάμεσα στα αμινοξέα 61-76 (Barkas et al 1988). Τελικά το κύριο τμήμα της MIR εντο πίστηκε ανάμεσα στα αμινοξέα 67-76 τόσο γιά στον ανθρώπινο όσο και στον Torpedo AChR (Tzartos et al 1988a.…”

Experimental autoimmune myasthenia gravis : target organ resistance and immunogenetics

“…Binding of antibodies to the MIR is highly dependent on the intact conformation of the AChR (76,(79)(80)(81). The MIR region is localized on the a-subunit and has been mapped to residues 67-76 by binding to synthetic peptides (82)(83)(84). The immunodominant epitope(s) are mainly formed by the residues 68-71 for which a hairpin like loop with a type I (3-turn is predicted (85).…”