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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-19042013-091132
Document
Author
Full name
Renato Brito Baleeiro
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Barbuto, Jose Alexandre Marzagao (President)
Calich, Vera Lucia Garcia
Câmara, Niels Olsen Saraiva
Coelho, Veronica Porto Carreiro de Vasconcellos
Kaneno, Ramon
Title in Portuguese
Apresentação cruzada e atividade imuno-estimuladora de células dendríticas pulsadas com antígenos particulados acoplados a um agonista de "Toll-like receptor".
Keywords in Portuguese
Adjuvantes imunológicos
Células dendríticas
Imunoterapia
Linfócitos
Vacinas
Abstract in Portuguese
As células dendríticas (DCs) são as principais células apresentadoras de antígenos (APCs). Foi proposto que as DCs selecionam os Ags que serão apresentados em MHC-II baseado na presença de ligantes para TLR na partícula fagocitada. Contudo, esse fenômeno não foi estudado em classe I. Assim, o objetivo deste estudo foi investigar se o acoplamento de Ags particulados a um agonista de TLR melhoraria a apresentação cruzada (AC) dos mesmos por DCs humanas tratadas com as moléculas acopladas. Nós vimos que a presença de um ligante de TLR no material fagocitado não contribuiu nem para a maturação do fagossomo, nem para a via endossômica de AC. A AC não envolve acidificação endossômica e depende de moléculas de MHC recém-sintetizadas do retículo endoplasmático. Nossos dados confirmam também a importância do estado de maturação das DCs para a indução de proliferação de LT CD8+, embora este não tenha sido associado com o nível de apresentação do complexo MHC-I/peptídeo, ou com as moléculas normalmente utilizadas para indicar a maturação das DCs.
Title in English
Cross-presentation and induction of immune response by dendritic cells pulsed with particulate antigens coupled to a "Toll-like receptor" agonist.
Keywords in English
Dendritic cells
Immune adjuvants
Immunotherapy
Lymphocytes
Vaccines
Abstract in English
Dendritic cells (DCs) are the main antigen presenting cells (APCs). It was proposed that DCs select the Ags that will be presented at their surfaces on class II based on the presence of a TLR-ligand on the cargo. However, the relevance of the coupling of the Ag to a TLR-ligand on class I was not yet addressed. Thus, the goal of this study was to investigate whether the coupling of particulate Ags to a TLR-agonist improve the cross-presentation (CP). We saw that the CP does not involve endosomal acidification and it relies on newly synthesized MHC-I molecules from the endoplasmic reticulum. Also, the presence of a TLR-ligand on the cargo neither contributed to the phagosome maturation nor to the endosomic route of CP. Furthermore, the maturation status of DCs was crucial for the induction of CD8+ T cells proliferation. Although the coupling of the Ag to the adjuvant has neither changed the expression of the markers related to maturation nor the presentation of the complex MHC-I/peptide at the DC surface, it affected its capacity of stimulating CD8+ T cells.
 
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Publishing Date
2013-05-24
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • BALEEIRO, Renato Brito, et al. Direct Activation of Human Dendritic Cells by Particle-Bound but Not Soluble MHC Class II Ligand [doi:10.1371/journal.pone.0063039]. PLoS ONE [online], 2013, vol. 8, n. 5, p. e63039.
  • BALEEIRO, Renato Brito, et al. Topical Vaccination with Functionalized Particles Targeting Dendritic Cells [doi:10.1038/jid.2013.79]. Journal of Investigative Dermatology [online], 2013.
All rights of the thesis/dissertation are from the authors
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