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Abstract:

BALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2β protein (TcP2β) develop a strong and specific antibody response against its 13 residue-long C-terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant β1-adrenergic stimulating activity. However, other animals that undergo similar immunizations seem tolerant to this epitope. To evaluate further the antibody response against the ribosomal P proteins, 25 BALB/c and 25 Swiss mice were immunized with TcP2β. From the 50 animals, 31 developed a positive anti-R13 response, whereas 19 were non-responsive. From the 31 anti-R13 positive mice, 25 had anti-R13 antibodies that recognized the discontinuous motif ExDDxGF, and their presence correlated with the recording of supraventricular tachycardia. The other six had anti-R13 antibodies but with a normal electrocardiographic recording. These anti-R13 antibodies recognized the motif DDxGF shared by mammals and T. cruzi and proved to be a true anti-P autoantibody because they were similar to those elicited in Swiss, but not in BALB/c mice, by immunization with the C-terminal portion of the mouse ribosomal P protein. Our results show that the recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the motif AESDE of the second extracellular loop of the β1-adrenergic receptor, setting the molecular basis for their pathogenic β1 adrenoceptor stimulating activity. © 2005 British Society for Immunology.

Registro:

Documento: Artículo
Título:The β1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2β protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition
Autor:Bergami, P.L.; Gómez, K.A.; Levy, G.V.; Grippo, V.; Baldi, A.; Levin, M.J.
Filiación:Laboratorio de Biologín Molecular de la Enfermedad de Chagas, Inst. Invest. en Ing. Genet./Biol. Molec.-Consejo Nac. de Invest. Cie./Tec. (INGEBI/CONICET)/CeGA, Centro de Genómica Aplicada-Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Biología y Medicina Experimental (IBYME), Buenos Aires, Argentina
Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular (INGEBI), Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina
Palabras clave:β1-adrenergic receptor; Pathogenic antibodies; Ribosomal P proteins; Trypanosoma cruzi; beta 1 adrenergic receptor; epitope; glutamylglutamylglutamylaspartylaspartylaspartylmethionylglycylphenylalanylglycylleucylphenylalanylaspartic acid; peptide; protein antibody; protein TcP2beta; protozoal protein; ribosome protein; unclassified drug; autoantibody; beta 1 adrenergic receptor; epitope; immunoglobulin G; protozoon antibody; recombinant protein; ribosome protein; adrenergic activity; amino acid sequence; animal experiment; animal model; antigen recognition; article; carboxy terminal sequence; controlled study; electrocardiography; epitope mapping; immune response; immunization; immunological tolerance; mouse; nonhuman; priority journal; protein analysis; protein motif; supraventricular tachycardia; Trypanosoma cruzi; animal; autoimmunity; Bagg albino mouse; Chagas disease; immunology; methodology; pathophysiology; Trypanosoma cruzi; Animals; Antibodies, Protozoan; Autoantibodies; Autoimmunity; Chagas Disease; Electrocardiography; Epitope Mapping; Epitopes; Immunoglobulin G; Mice; Mice, Inbred BALB C; Protozoan Proteins; Receptors, Adrenergic, beta-1; Recombinant Proteins; Ribosomal Proteins; Trypanosoma cruzi
Año:2005
Volumen:142
Número:1
Página de inicio:140
Página de fin:147
DOI: http://dx.doi.org/10.1111/j.1365-2249.2005.02885.x
Título revista:Clinical and Experimental Immunology
Título revista abreviado:Clin. Exp. Immunol.
ISSN:00099104
CODEN:CEXIA
CAS:immunoglobulin G, 97794-27-9; Antibodies, Protozoan; Autoantibodies; Epitopes; Immunoglobulin G; Protozoan Proteins; Receptors, Adrenergic, beta-1; Recombinant Proteins; Ribosomal Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00099104_v142_n1_p140_Bergami

Referencias:

  • Elizari, M.V., Chiale, P.A., Pharmacologic treatment of arrhythmias related to chronic Chagas' heart disease (2000) Arrhytmia Management in Chagas' Disease, pp. 95-116. , Tentori MC, Segura E, Hayes DL, eds. Armonk, New York: Futura Publishing Co
  • Chiale, P.A., Ferrari, I., Mahler, E., Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction (2001) Circulation, 103, pp. 1765-1771
  • Borda, E., Sterin-Borda, L., Antiadrenergic and muscarinic receptor antibodies in Chagas' cardiomyopathy (1996) Int J Cardiol, 54, pp. 149-156
  • Kierszenbaum, F., Chagas' disease and the autoimmunity hypothesis (1999) Clin Microbiol Rev, 12, pp. 210-223
  • Kaplan, D., Ferrari, I., Lopez Bergami, P., Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas' disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus (1997) Proc Natl Acad Sci USA, 94, pp. 10301-10306
  • Elies, R., Ferrari, I., Wallukat, G., Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease (1996) J Immunol, 157, pp. 4203-4211
  • Masuda, M., Levin, M.J., Farias De Oliveira, S., Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens (1998) FASEB J, 12, pp. 1551-1558
  • Lopez Bergami, P., Scaglione, J., Levin, M.J., Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic (2001) FASEB J, 15, pp. 2602-2612
  • Lopez Bergami, P., Cabeza Meckert, P., Kaplan, D., Immunization with recombinant Trypanosoma cruzi ribosomal P2β protein induces changes in the electrocardiogram of immunized mice (1997) FEMS Immunol Med Microbiol, 18, pp. 75-85
  • Muller, S., Couppez, M., Briand, J.P., Gordon, J., Sautiere, P., Van Regenmortel, M.H., Antigenic structure of histone H2B (1985) Biochim Biophys Acta, 827, pp. 235-246
  • Levin, M.J., Vazquez, M., Kaplan, D., Schijman, A.G., The Trypanosoma cruzi ribosomal P protein family: Classification and antigenicity (1993) Parasitol Today, 9, pp. 381-384
  • Elkon, K., Bonfa, E., Llovet, R., Danho, W., Weissbach, H., Brot, N., Properties of the ribosomal P2 protein autoantigen are similar to those of foreign protein antigens (1988) Proc Natl Acad Sci USA, 85, pp. 5186-5189
  • Magnusson, Y., Hoyer, S., Lengagne, R., Antigenic analysis of the second extra-cellular loop of the human beta-adrenergic receptors (1989) Clin Exp Immunol, 78, pp. 42-48
  • Mesri, E., Levitus, G., Hontebeyrie-Joskowicz, M., Major Trypanosoma cruzi determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope (1990) J Clin Microbiol, 28, pp. 1219-1224
  • Hines, J.J., Weissbach, H., Brot, N., Elkon, K., Anti-P autoantibody production requires P1/P2 as immunogen but is not driven by exogenous self-antigen in MLR mice (1991) J Immunol, 146, pp. 3386-3395
  • Sepulveda, P., Liegeard, P., Wallukat, G., Levin, M.J., Hontebeyrie, M., Modulation of cardiocyte functional activity by antibodies against Trypanosoma cruzi ribosomal P2 protein C-terminus (2000) Infect Immunol, 68, pp. 5114-5119
  • Elkon, K., Bonfa, E., Skeky, S., Ribosomal protein autoantibodies in systemic lupus erythematosus (1987) Bioessays, 7, pp. 258-261
  • Mahler, E., Hoebeke, J., Levin, M.J., Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2 β protein in patients with chronic Chagas' heart disease (2004) Clin Exp Immunol, 136, pp. 527-534
  • Mahler, E., (2002) Rol de Las Proteínas P de Trypanosoma Cruzi en la Generación de Anticuerpos Con Autorreactividad Funcional en la Cardiomiopatía Crónica Chagásica, , PhD thesis, University of Buenos Aires
  • Mahler, M., Kessenbrock, K., Raats, J., Williams, R., Fritzler, M.J., Bluthner, M., Characterization of the human autoimmune response to the major C-terminal epitope of the ribosomal P proteins (2003) Mol Med, 81, pp. 194-204
  • Zampieri, S., Mahler, M., Bluthner, M., Recombinant anti-P protein autoantibodies isolated from a human autoimmune library: Reactivity, specificity and epitope recognition (2003) Cell Mol Life Sci, 60, pp. 588-598
  • Sun, B., Rizzo, L.V., Sun, S.-H., Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response (1997) J Immunol, 159, pp. 1004-1011
  • Scott, P., IFN-γ modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis (1991) J Immunol, 147, pp. 3149-3155
  • Keane-Myers, A., Nickell, S.P., Role of IL-4 and IFN-γ in modulation of immunity to Borrelia burgdorferi in mice (1995) J Immunol, 155, pp. 2020-2028

Citas:

---------- APA ----------
Bergami, P.L., Gómez, K.A., Levy, G.V., Grippo, V., Baldi, A. & Levin, M.J. (2005) . The β1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2β protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition. Clinical and Experimental Immunology, 142(1), 140-147.
http://dx.doi.org/10.1111/j.1365-2249.2005.02885.x
---------- CHICAGO ----------
Bergami, P.L., Gómez, K.A., Levy, G.V., Grippo, V., Baldi, A., Levin, M.J. "The β1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2β protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition" . Clinical and Experimental Immunology 142, no. 1 (2005) : 140-147.
http://dx.doi.org/10.1111/j.1365-2249.2005.02885.x
---------- MLA ----------
Bergami, P.L., Gómez, K.A., Levy, G.V., Grippo, V., Baldi, A., Levin, M.J. "The β1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2β protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition" . Clinical and Experimental Immunology, vol. 142, no. 1, 2005, pp. 140-147.
http://dx.doi.org/10.1111/j.1365-2249.2005.02885.x
---------- VANCOUVER ----------
Bergami, P.L., Gómez, K.A., Levy, G.V., Grippo, V., Baldi, A., Levin, M.J. The β1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2β protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition. Clin. Exp. Immunol. 2005;142(1):140-147.
http://dx.doi.org/10.1111/j.1365-2249.2005.02885.x