Molecular mimicry between a monoclonal antibody and one subunit of crotoxin, a heterodimeric phospholipase A(2) neurotoxin

Crotoxin is a heterodimeric phospholipase Ap neurotoxin formed by the non-c ovalent association of an acidic and non-toxic subunit, CA, and a basic and weakly toxic phospholipase Aar CB, The two subunits behave in a synergisti c manner. CA enhances the lethal potency of CB by increasing its selectivit y of action. The mAb A-56.36, directed against the non-toxic subunit CA, wa s previously shown to neutralize crotoxin toxicity by dissociating the crot oxin complex. In the present report, a polypeptide sequence similarity was observed between some CDRs of mAb A-56.36 and two regions of CB (pos. 60-80 and 95-110), Phage displayed peptides corresponding to VH2 and VH3 of mAb A-56.36 and to their homologous sequences in CB bind CA to different extent s. This observation shows that mAb A-56.36 interacts with a region of CA in volved in its interaction with CB, therefore mimicking the binding of CB to CA. A similar approach was used to determine the regions of ammodytoxin A and of agkistrodotoxin, two phospholipase A(2) neurotoxins similar to CB, w hich are involved in the formation of heterocomplexes with CA. The analysis of these data contributes to the determination of stretches of amino acids which could constitute the paratope of mAb A-56.36, as well as the region of association of CB with CA in crotoxin.