Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2β protein and the human β1 adrenergic receptor

Antibodies from patients with Chagas heart disease and monoclonal antibodies (or mAb) to the carboxy-terminal end (B cell epitope R13) of the ribosomal P2β protein of Trypanosoma cruzi (TcP2β) cross-react with the β1 adrenergic receptor (β1-AR). Two single-chain Fv fragments (scFv) C5 and B7 derived from the variable regions of the anti-R13 mAb 17.2 were expressed. scFv C5 was a dimer and bound to TcP2β with an affinity of Kd = 8 nM, whereas scFv B7 was monomeric and had less affinity than scFv C5 for TcP2β, Kd = 46 nM. The affinity constant of scFv C5 to the second extracellular loop of the human β1-AR was of 10 μM. Moreover, scFv C5 induced an increase in cAMP levels of CHO-K cells transfected with the human β1-AR; scFv B7 had no effect but blocked isoproterenol stimulation. The agonist-like activity of scFv C5 and the antagonist activity of scFv B7 were both confirmed in vivo on heart beating frequency after their passive transfer to mice. Molecular modeling of the variable region of mAb 17.2 indicated...