Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.

Brucella spp. Lumazine Synthase (BLS) is a highly immunogenic and stable homodecameric protein which has the ability to activate dendritic cells. It can be used to generate decameric chimeras by adding the peptide sequence to the monomer. Immunization with these chimeras induces a long-lasting and s...

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Autor principal: Rossi, Andrés Hugo
Otros Autores: Alzogaray, Vanina Andrea
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2016
Materias:
BLS
Persistencia
Humoral
Lumazina sintasa
Brucella spp.
Ciencias de la salud
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1414
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1414.dir/1414.PDF
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
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spelling I28-R145-HWA_14142019-09-25 Brucella spp. Lumazine Synthase (BLS) is a highly immunogenic and stable homodecameric protein which has the ability to activate dendritic cells. It can be used to generate decameric chimeras by adding the peptide sequence to the monomer. Immunization with these chimeras induces a long-lasting and strong humoral response against BLS and the peptide; by these means BLS can be used as a carrier. In this work we aimed to study the persistence of BLS in the immunized animal and how this particular protein is processed as an antigen, as two of the main aspects that may play a role in developing the above mentioned humoral immune response. We were able to show that BLS associates with the plasma membrane of dendritic cells, enters the cell via macropinocytosis and co-localizes with TLR4. BLS is mostly processed by the exogenous pathway but a small portion was not associated with this pathway. BLS persists for 96 hours in vitro in a higher amount of dendritic cells in comparison with a control antigen and still persists in cells of the draining lymph node for 14 days post immunization. \nBLS remains in the immunized animal for a longer period than the control antigen, however this probably does not explain the persistence of the humoral response.\nThis work contributes to get a better understanding of the immunological processes that allow BLS to act as a carrier and it might be use as a powerful tool for the development and improvement of vaccine platforms. Fil: Rossi, Andrés Hugo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Alzogaray, Vanina Andrea Baldi, Pablo Facultad de Farmacia y Bioquímica Berguer, Paula Mercedes Rossi, Andrés Hugo 2016-03-31 La lumazina sintasa de Brucella spp. (BLS) es una proteína homodecamérica altamente estable y con la capacidad de activar células dendríticas vía TLR4. Puede ser utilizada para generar quimeras decaméricas insertando la secuencia de péptidos en cada monómero. La inmunización con estas quimeras induce una respuesta humoral fuerte y persistente anti-BLS y anti-péptido; de esta manera BLS constituye un excelente carrier. En el presente trabajo estudiamos la persistencia de BLS en el animal inmunizado y su procesamiento antigénico como parte de las características que pueden otorgar a esta proteína la capacidad de inducir tan extensa respuesta humoral. Se demostró que BLS se asocia a la membrana plasmática de las células dendríticas, ingresa vía macropinocitosis y colocaliza con TLR4. BLS se procesa principalmente por la vía para antígenos exógenos, pero una porción menor no se asocia a esa vía. BLS persiste in vitro por 96 hs en un mayor número de células dendríticas que un antígeno control y persiste en las células del ganglio drenante aún 14 días p.i. \nLa persistencia de BLS in vivo resulta significativamente mayor a la del antígeno control, sin embargo no justificaría la persistencia de la respuesta humoral.\nEl aporte del presente trabajo contribuye al entendimiento de los procesos inmunológicos que permiten a BLS actuar como carrier y constituye una potente herramienta para el diseño y mejoramiento de plataformas de vacunas en desarrollo. application/pdf Álvarez, Élida Moron, Víctor Fernández, Marisa BLS Persistencia Humoral Lumazina sintasa Brucella spp. spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la salud Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp. info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1414 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1414.dir/1414.PDF
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic BLS
Persistencia
Humoral
Lumazina sintasa
Brucella spp.
Ciencias de la salud
spellingShingle BLS
Persistencia
Humoral
Lumazina sintasa
Brucella spp.
Ciencias de la salud
Rossi, Andrés Hugo
Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.
topic_facet BLS
Persistencia
Humoral
Lumazina sintasa
Brucella spp.
Ciencias de la salud
description Brucella spp. Lumazine Synthase (BLS) is a highly immunogenic and stable homodecameric protein which has the ability to activate dendritic cells. It can be used to generate decameric chimeras by adding the peptide sequence to the monomer. Immunization with these chimeras induces a long-lasting and strong humoral response against BLS and the peptide; by these means BLS can be used as a carrier. In this work we aimed to study the persistence of BLS in the immunized animal and how this particular protein is processed as an antigen, as two of the main aspects that may play a role in developing the above mentioned humoral immune response. We were able to show that BLS associates with the plasma membrane of dendritic cells, enters the cell via macropinocytosis and co-localizes with TLR4. BLS is mostly processed by the exogenous pathway but a small portion was not associated with this pathway. BLS persists for 96 hours in vitro in a higher amount of dendritic cells in comparison with a control antigen and still persists in cells of the draining lymph node for 14 days post immunization. \nBLS remains in the immunized animal for a longer period than the control antigen, however this probably does not explain the persistence of the humoral response.\nThis work contributes to get a better understanding of the immunological processes that allow BLS to act as a carrier and it might be use as a powerful tool for the development and improvement of vaccine platforms.
author2 Alzogaray, Vanina Andrea
author_facet Alzogaray, Vanina Andrea
Rossi, Andrés Hugo
format Tesis doctoral
Tesis doctoral
acceptedVersion
author Rossi, Andrés Hugo
author_sort Rossi, Andrés Hugo
title Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.
title_short Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.
title_full Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.
title_fullStr Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.
title_full_unstemmed Caracterización del procesamiento antigénico y la persistencia de la proteína Lumazina Sintasa de Brucella spp.
title_sort caracterización del procesamiento antigénico y la persistencia de la proteína lumazina sintasa de brucella spp.
publisher Facultad de Farmacia y Bioquímica
publishDate 2016
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1414
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1414.dir/1414.PDF
work_keys_str_mv AT rossiandreshugo caracterizaciondelprocesamientoantigenicoylapersistenciadelaproteinalumazinasintasadebrucellaspp
_version_ 1766017473218347008

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