Human recombinant antibodies against Trypanosoma cruzi ribosomal P2 b protein

GRIPPO VANINA; NIBORSKI LL; GOMEZ KA; LEVIN MJ

PARASITOLOGY

CAMBRIDGE UNIV PRESS

Año: 2011 p. 1 - 12

0031-1820

Patients with chronic Chagas´ Heart Disease (cChHD) develop an antibody response that is suspected to be involved in the cardiac pathogenesis. The response against Trypanosoma cruzi ribosomal P proteins is of particular interest, as these antibodies can cross-react with host cardiac receptors causing electrophysiological alterations. To better understand the humoral anti-P response we constructed a single-chain variable fragment library derived from a cChHD patient. The variable heavy and light regions were amplified from bone-marrow RNA and subcloned into the vector pComb3X. The phage library was subsequently panned against T. cruzi ribosomal P2b protein (TcP2b). We obtained 3 different human recombinant antibodies that specifically reacted with TcP2b in ELISA and Western blots. Two of them reacted with the C-terminal region of TcP2b, peptide R13, as the recombinant autoanti-P antibodies from Systemic Lupus Erythematosus (SLE) patients. Interestingly, the third one was specific for TcP2b but did not recognize R13, confirming the specific nature of the anti-P response in Chagas disease. Neither sequence nor VH usage similarities between Chagas and SLE anti-P autoantibodies were observed. Herein, the first human mAbs against TcP2b have been obtained and characterized showing that the humoral anti-P response is directed against the parasite and does not include an autoimmune component.