Monoclonal antibodies antibodies against the C-terminal region of Trypanosoma cruzi ribosomal P0 protein exert only β1-adrenergic but not muscarinic functional activity

TASSO, LAURA M; CHIRIVI, RENATO; SCHIMKE, INGOLF; WALLUKAT, GERARD; SIMONETTI, LEANDRO; LONGHI, SILVIA A.; RAAT, JOS; GOMEZ, KARINA A

Buenos Aires

Congreso; I Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Protozoologia y Enfermedades Parasitarias (SAP)

The chronic Chagas heart disease (cChHD) is the most frequent and severe manifestation of T. cruzi infection. Its pathogenesis is currently explained by two, non-mutually exclusive hypotheses: the immune response associated with parasite persistence and the molecular mimicry between host and parasite proteins. In this regard, we have previously demonstrated the presence of high antibody (Ab) levels against T. cruzi ribosomal P proteins, TcP0 and TcP2β proteins, which bear similarities with cardiac receptors β1 adrenergic (β1-AR) and muscarinic (M2-R), in cChHD patients´ sera. Since immunization of mice with TcP0 induced Abs against its C-terminal region (P015 peptide) that bind to and stimulate both types of cardiac receptors, we decided to explore its functional activity by the generation of anti-P015 monoclonal Abs (mAbs). After immunization of BALB/c and autoimmune-prone mice with P015-BSA, three anti-P015 mAbs were obtained. All of them recognized P015 peptide and P0 protein, as well as the other Tc ribosomal P proteins in ELISA and Western blot. Immunofluorescence assay showed a positive staining in the cytoplasm of the different T. cruzi stages. The functional activity of these mAbs was measured by pharmacological assay based on primary cultures of neonatal rat cardiomyocytes. Results showed that the mAbs induced a positive chronotropic effect (p