Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system [Elektronisk resurs]

• Background: To deeply understand the role of antibodies in the context of Trypanosoma cruzi infection, we decided to characterize A2R1, a parasite antibody selected from single-chain variable fragment (scFv) phage display libraries constructed from B cells of chronic Chagas heart disease patients. Methods: Immunoblot, ELISA, cytometry, immunofluorescence and immunohistochemical assays were used to characterize A2R1 reactivity. To identify the antibody target, we performed an immunoprecipitation and two-dimensional electrophoresis coupled to mass spectrometry and confirmed A2R1 specific interaction by producing the antigen in different expression systems. Based on these data, we carried out a comparative in silico analysis of the protein targets orthologues, focusing mainly on post-translational modifications. Findings: A2R1 recognizes a parasite protein of similar to 50 kDa present in all life cycle stages of T. cruzi, as well as in other members of the kinetoplastid family, showing a defined immunofluorescence labeling pattern consistent with the cytoskeleton. A2R1 binds to tubulin, but this interaction relies on its post-translational modifications. Interestingly, this antibody also targets mammalian tubulin only present in brain, staining in and around cell bodies of the human peripheral and central nervous system. Interpretation: Our findings demonstrate for the first time the existence of a human antibody against T. cruzi tubulin capable of cross-reacting with a human neural protein. This work re-emphasizes the role of molecular mimicry between host and parasitic antigens in the development of pathological manifestations of T. cruzi infection. 

Ämnesord

Natural Sciences  (hsv)

Biological Sciences  (hsv)

Biochemistry and Molecular Biology  (hsv)

Naturvetenskap  (hsv)

Biologiska vetenskaper  (hsv)

Biokemi och molekylärbiologi  (hsv)

Genre

government publication  (marcgt)

Indexterm och SAB-rubrik

Chagas disease

Phage-display

Tubulin

Molecular mimicry

Post-translational modification

Digestive system