Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system.

NIBORSKI LL; POTENZA M; CHIRIVI RGS; SIMONETTI L; OSSOWSKI MS; GRIPPO V; MAY M; STAQUICINI DI; PARODI-TALICE A; ROBELLO C; COMINI M; ALONSO G; RAATS J; GOMEZ KA

EBioMedicine

Elsevier B.V.

Año: 2021 vol. 63

2352-3964

Background: To deeply understand the role of antibodies in the context ofTrypanosoma cruzi infection, we decided to characterize A2R1, a parasite antibodyselected from single-chain variable fragment (scFv) phage display librariesconstructed from B cells of chronic Chagas heart disease patients.Methods: Immunoblot, ELISA, cytometry, immunofluorescence andimmunohistochemical assays were used to characterize A2R1 reactivity. Toidentify the antibody target, we performed an immunoprecipitation and twodimensionalelectrophoresis coupled to mass spectrometry and confirmed A2R1specific interaction by producing the antigen in different expression systems.Based on these data, we carried out a comparative in silico analysis of the proteintarget´s orthologues, focusing mainly on post-translational modifications.Findings: A2R1 recognizes a parasite protein of ~50 kDa present in all life cyclestages of T. cruzi, as well as in other members of the kinetoplastid family, showinga defined immunofluorescence labelling pattern consistent with the cytoskeleton.A2R1 binds to tubulin, but this interaction relies on its post-translationalmodifications. Interestingly, this antibody also targets mammalian tubulin onlypresent in brain, staining in and around cell bodies of the human peripheral andcentral nervous system.Interpretation: Our findings demonstrate for the first time the existence of a humanantibody against T. cruzi tubulin capable of cross-reacting with a human neuralprotein. This work re-emphasizes the role of molecular mimicry between host and parasitic antigens in the development of pathological manifestations of T. cruziinfection (Aceptado 2020, Publicado Enero 2021)