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Abstract:

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 P2β protein (TcP2β). We obtained 3 different human recombinant antibodies that specifically reacted with TcP2β in ELISA and Western blots. Two of them reacted with the C-terminal region of TcP2β, peptide R13, as the recombinant autoanti-P antibodies from Systemic Lupus Erythematosus (SLE) patients. Interestingly, the third one was specific for TcP2β 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 TcP2β have been obtained and characterized showing that the humoral anti-P response is directed against the parasite and does not include an autoimmune component. Copyright © Cambridge University Press 2011.

Registro:

Documento: Artículo
Título:Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein
Autor:Grippo, V.; Niborski, L.L.; Gomez, K.A.; Levin, M.J.
Filiación:Laboratory of Molecular Biology of Chagas' Disease, Institute for Genetic Engineering and Molecular Biology (INGEBI), CONICET-UBA, 1428 Ciudad Autónoma de Buenos Aires, Argentina
Laboratorio de Biología Molecular de la Enfermedad de Chagas, INGEBI, Vuelta de Obligado 2490, 1428-Ciudad Autónoma de Buenos Aires, Argentina
Palabras clave:Chagas disease; human recombinant antibodies; phage display; ribosomal P protein; Trypanosoma cruzi; autoantibody; complementary DNA; glutamylglutamylglutamylaspartylaspartylaspartylmethionylglycylphenylalanylglycy lleucylphenylalanylaspartic acid; glutathione transferase; human monoclonal antibody; human recombinant antibody; immunoglobulin G; immunoglobulin heavy chain; immunoglobulin light chain; maltose binding protein; peptide derivative; protozoal protein; protozoon antibody; recombinant antibody; ribosome protein; ribosome RNA; RNA; single chain fragment variable antibody; trypanosoma cruzi ribosomal p2 beta protein; unclassified drug; adult; amino acid sequence; antibody response; antibody specificity; antigen recognition; article; bone marrow cell; carboxy terminal sequence; Chagas disease; clinical article; combinatorial library; controlled study; enzyme linked immunosorbent assay; gene expression; human; human cell; molecular cloning; nonhuman; peptide synthesis; phage display; polymerase chain reaction; priority journal; sequence alignment; sequence analysis; Trypanosoma cruzi; Western blotting; Amino Acid Sequence; Antibodies, Protozoan; Bone Marrow; Chagas Cardiomyopathy; Chagas Disease; Enzyme-Linked Immunosorbent Assay; Gene Library; Humans; Lupus Erythematosus, Systemic; Phosphoproteins; Protozoan Proteins; Recombinant Proteins; Ribosomal Proteins; Sequence Alignment; Trypanosoma cruzi; Trypanosoma cruzi
Año:2011
Volumen:138
Número:6
Página de inicio:736
Página de fin:747
DOI: http://dx.doi.org/10.1017/S0031182011000175
Título revista:Parasitology
Título revista abreviado:Parasitology
ISSN:00311820
CODEN:PARAA
CAS:RNA, 63231-63-0; glutathione transferase, 50812-37-8; immunoglobulin G, 97794-27-9; single chain fragment variable antibody, 334577-34-3, 334577-38-7; Antibodies, Protozoan; Phosphoproteins; Protozoan Proteins; Recombinant Proteins; Ribosomal Proteins; phosphoprotein P2, ribosomal
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00311820_v138_n6_p736_Grippo

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Citas:

---------- APA ----------
Grippo, V., Niborski, L.L., Gomez, K.A. & Levin, M.J. (2011) . Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein. Parasitology, 138(6), 736-747.
http://dx.doi.org/10.1017/S0031182011000175
---------- CHICAGO ----------
Grippo, V., Niborski, L.L., Gomez, K.A., Levin, M.J. "Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein" . Parasitology 138, no. 6 (2011) : 736-747.
http://dx.doi.org/10.1017/S0031182011000175
---------- MLA ----------
Grippo, V., Niborski, L.L., Gomez, K.A., Levin, M.J. "Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein" . Parasitology, vol. 138, no. 6, 2011, pp. 736-747.
http://dx.doi.org/10.1017/S0031182011000175
---------- VANCOUVER ----------
Grippo, V., Niborski, L.L., Gomez, K.A., Levin, M.J. Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein. Parasitology. 2011;138(6):736-747.
http://dx.doi.org/10.1017/S0031182011000175