Seminario INGEBI

Recombinant single-chain variable fragment (scFv) antibodies: from the patient with Chagas disease to the bench.

Lunes 7 de Junio

Dra. Karina Gómez

INGEBI CONICET

Infection with the protozoan parasite Trypanosoma cruzi evolves to a chronic disease which is characterized by a broad humoral immune response, eventually resulting in cardiac and/or digestive alterations in patients. We will discuss the characterization of two T. cruzi antibodies named as A2R1 and 6B6, which have been selected from a single-chain Fv phage display library constructed from chronic Chagas heart disease patient B-cells. ScFv A2R1 binds to T. cruzi tubulin and cross-reacts with a ~50 kDa protein only present in mammalian neural tissue. Interestingly, the antibody binding site on tubulin contains one of the post-translational modifications present in trypanosomatids, and this could be the explanation why the antibody specifically interacts with its neuronal isotype. Our finding re-emphases the role of molecular mimicry between host and parasitic antigens in the development of clinical and pathological manifestations of T. cruzi infection. ScFv 6B6 binds a hypothetical protein of ~320 KDa present in different strains of T. cruzi, but has no evident homologous in other eukaryotes. Preliminary results showing that scFv 6B6 target protein is only recognized by sera from patients with chronic Chagas Disease, but not from individuals infected with Leishmania were enlightening, and tempt us to investigate the potential useful of this protein as specific diagnostic marker for T. cruzi infection.