Mimicry between receptors and antibodies. Identification of snake toxin determinants recognized by the acetylcholine receptor and an acetylcholine receptor-mimicking monoclonal antibody.
In several instances, a monoclonal antibody raised against a receptor ligand has been claimed to mimic the ligand receptor. Thus, a specific monoclonal antibody (Malpha2-3) raised against a short-chain toxin from snake was proposed to mimic the nicotinic acetylcholine receptor (AChR) (). Further confirming this mimicry, we show that (i) like AChR, Malpha2-3 elicits anti-AChR antibodies, which in turn elicit anti-toxin antibodies; and (ii) the region 106-122 of the alpha-chain of AChR shares 66% primary structure identity with complementarity-determining regions of Malpha2-3. Also, a mutational analysis of erabutoxin a reveals that the epitope recognized by Malpha2-3 consists of 10 residues, distributed within the three toxin loops. Eight of these residues also belong to the 10-residue epitope recognized by AChR, a result that offers an explanation as to the functional similarities between the receptor and the antibody. Strikingly, however, most of the residues common to the two epitopes contribute differentially to the energetic formation of the antibody-toxin and the receptor-toxin complexes. Together, the data suggest that the mimicry between AChR and Malpha2-3 is partial only.
Ducancel
F
F
Département d'Ingénierie et d'Etudes des Protéines, DSV, CEA, Saclay, 91191 Gif-sur-Yvette, France.
Mérienne
K
K
Fromen-Romano
C
C
Trémeau
O
O
Pillet
L
L
Drevet
P
P
Zinn-Justin
S
S
Boulain
J C
JC
Ménez
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D003039:Cobra Neurotoxin Proteins / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D003472:Curare / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D004870:Erabutoxins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*; D016415:Sequence Alignment; D014101:Torpedo
D000911:Antibodies, Monoclonal; D003039:Cobra Neurotoxin Proteins; D000939:Epitopes; D011950:Receptors, Cholinergic; D004870:Erabutoxins; C025154:alpha-cobratoxin; D003472:Curare