This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.CHAGAS DISEASE, CAUSED by the protozoan parasite Trypanosoma cruzi, affects 18 '20 million people in Latin America. The most severe manifestation of this infection is chronic Chagas heart disease (cChHD). Antibodies from patients with Chagas heart disease and monoclonal antibodies (or mAb) to the carboxy-terminal end (B cell epitope R13) of the ribosomal P2 x protein of Trypanosoma cruzi (TcP2 x) cross-react with the x1 adrenergic receptor ( x1-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 TcP2 x with an affinity of Kd = 8 nM, whereas scFv B7 was monomeric and had less affinity than scFv C5 for TcP2 x, Kd = 46 nM. The affinity constant of scFv C5 to the second extracellular loop of the human x1-AR was of 10 M.
The aim of this study is to elucidate the structural basis of TcP2B and b1-AR recognition by C5 and B7 monoclonal antibody.
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