Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein
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 c...
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todo:paper_00311820_v138_n6_p736_Grippo2023-10-03T14:41:14Z Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein Grippo, V. Niborski, L.L. Gomez, K.A. Levin, M.J. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00311820_v138_n6_p736_Grippo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Grippo, V. Niborski, L.L. Gomez, K.A. Levin, M.J. Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Grippo, V. Niborski, L.L. Gomez, K.A. Levin, M.J. |
| author_facet |
Grippo, V. Niborski, L.L. Gomez, K.A. Levin, M.J. |
| author_sort |
Grippo, V. |
| title |
Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein |
| title_short |
Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein |
| title_full |
Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein |
| title_fullStr |
Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein |
| title_full_unstemmed |
Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein |
| title_sort |
human recombinant antibodies against trypanosoma cruzi ribosomal p2β protein |
| url |
http://hdl.handle.net/20.500.12110/paper_00311820_v138_n6_p736_Grippo |
| work_keys_str_mv |
AT grippov humanrecombinantantibodiesagainsttrypanosomacruziribosomalp2bprotein AT niborskill humanrecombinantantibodiesagainsttrypanosomacruziribosomalp2bprotein AT gomezka humanrecombinantantibodiesagainsttrypanosomacruziribosomalp2bprotein AT levinmj humanrecombinantantibodiesagainsttrypanosomacruziribosomalp2bprotein |
| _version_ |
1807322635430789120 |