MONOCLONAL ANTIBODIES AGAINST THE C-TERMINAL REGION OF TRYPANOSOMA CRUZI RIBOSOMAL P0 PROTEIN EXERT ONLY Β1-ADRENERGIC BUT NOT MUSCARINIC FUNCTIONAL ACTIVITY

LAURA MÓNICA TASSO; RENATO CHIRIVI; INGOLF SCHIMKE; GERD WALLUKAT; LEANDRO SIMONETTI; LONGHI SILVIA A; JOS RAATS; GOMEZ KARINA A

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS-XXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE PROTOZOOLOGÍA; 2017

Sociedad Argentina de Protozoologia

The chronic Chagas heart disease (cChHD) is the most frequentand severe manifestation of T. cruzi infection. Its pathogenesis iscurrently explained by two, non-mutually exclusive hypotheses: theimmune response associated with parasite persistence and the molecularmimicry 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 TcP2βproteins, which bear similarities with cardiac receptors β1 adrenergic(β1-AR) and muscarinic (M2-R), in cChHD patients´ sera. Sinceimmunization of mice with TcP0 induced Abs against its C-terminalregion (P015 peptide) that bind to and stimulate both types of cardiacreceptors, we decided to explore its functional activity by thegeneration of anti-P015 monoclonal Abs (mAbs). After immunizationof BALB/c and autoimmune-prone mice with P015-BSA, threeanti-P015 mAbs were obtained. All of them recognized P015 peptideand P0 protein, as well as the other Tc ribosomal P proteinsin ELISA and Western blot. Immunofluorescence assay showed apositive staining in the cytoplasm of the different T. cruzi stages. Thefunctional activity of these mAbs was measured by pharmacologicalassay based on primary cultures of neonatal rat cardiomyocytes.Results showed that the mAbs induced a positive chronotropic effect(p