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Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis
Background: A safe and effective vaccine against human leishmaniasis still requires the identification of better antigens for immunization and adequate models to evaluate the immune response. To support vaccine development, this work tested the immunogenicity of 10 different peptides derived from th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033680/ https://www.ncbi.nlm.nih.gov/pubmed/32117204 http://dx.doi.org/10.3389/fimmu.2019.03145 |
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author | e Silva, Rafael de Freitas de Oliveira, Beatriz Coutinho da Silva, Ailton Alvaro Brelaz de Castro, Maria Carolina Accioly Ferreira, Luiz Felipe Gomes Rebello Hernandes, Marcelo Zaldini de Brito, Maria Edileuza Felinto de-Melo-Neto, Osvaldo Pompílio Rezende, Antônio Mauro Pereira, Valéria Rêgo Alves |
author_facet | e Silva, Rafael de Freitas de Oliveira, Beatriz Coutinho da Silva, Ailton Alvaro Brelaz de Castro, Maria Carolina Accioly Ferreira, Luiz Felipe Gomes Rebello Hernandes, Marcelo Zaldini de Brito, Maria Edileuza Felinto de-Melo-Neto, Osvaldo Pompílio Rezende, Antônio Mauro Pereira, Valéria Rêgo Alves |
author_sort | e Silva, Rafael de Freitas |
collection | PubMed |
description | Background: A safe and effective vaccine against human leishmaniasis still requires the identification of better antigens for immunization and adequate models to evaluate the immune response. To support vaccine development, this work tested the immunogenicity of 10 different peptides derived from the proteome of Leishmania braziliensis, which were selected by their in silico affinity to MHC complexes. Research design and Methods: Comparative cell proliferation assays were performed by culturing, in the presence of each peptide, PBMC cells from subclinical subjects (SC), cutaneous leishmaniasis patients with active disease (AD), post-treatment (PT) individuals, and healthy controls. Culture supernatants were then used for Th1, Th2, and Th17 cytokine measurements. Cells from selected PT samples were also used to assess the expression, by T cells, of the T-bet Th1 transcription factor. Results: A robust cell proliferation was observed for the SC group, for all the tested peptides. The levels of Th1 cytokines were peptide-dependent and had substantial variations between groups, where, for instance, IFN-γ and TNF levels were some of the highest, particularly on PT cultures, when compared to IL-2. On the other hand, Th2 cytokines displayed much less variation. IL-6 was the most abundant among all the evaluated cytokines while IL-4 and IL-10 could be found at much lower concentrations. IL-17 was also detected with variations in SC and AD groups. T-bet was up-regulated in CD4(+) and CD8(+) T cells from the PT group after stimulation with all peptides. Conclusions: The peptide epitopes can differentially stimulate cells from SC, AD, and PT individuals, leading to distinct immune responses. |
format | Online Article Text |
id | pubmed-7033680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70336802020-02-28 Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis e Silva, Rafael de Freitas de Oliveira, Beatriz Coutinho da Silva, Ailton Alvaro Brelaz de Castro, Maria Carolina Accioly Ferreira, Luiz Felipe Gomes Rebello Hernandes, Marcelo Zaldini de Brito, Maria Edileuza Felinto de-Melo-Neto, Osvaldo Pompílio Rezende, Antônio Mauro Pereira, Valéria Rêgo Alves Front Immunol Immunology Background: A safe and effective vaccine against human leishmaniasis still requires the identification of better antigens for immunization and adequate models to evaluate the immune response. To support vaccine development, this work tested the immunogenicity of 10 different peptides derived from the proteome of Leishmania braziliensis, which were selected by their in silico affinity to MHC complexes. Research design and Methods: Comparative cell proliferation assays were performed by culturing, in the presence of each peptide, PBMC cells from subclinical subjects (SC), cutaneous leishmaniasis patients with active disease (AD), post-treatment (PT) individuals, and healthy controls. Culture supernatants were then used for Th1, Th2, and Th17 cytokine measurements. Cells from selected PT samples were also used to assess the expression, by T cells, of the T-bet Th1 transcription factor. Results: A robust cell proliferation was observed for the SC group, for all the tested peptides. The levels of Th1 cytokines were peptide-dependent and had substantial variations between groups, where, for instance, IFN-γ and TNF levels were some of the highest, particularly on PT cultures, when compared to IL-2. On the other hand, Th2 cytokines displayed much less variation. IL-6 was the most abundant among all the evaluated cytokines while IL-4 and IL-10 could be found at much lower concentrations. IL-17 was also detected with variations in SC and AD groups. T-bet was up-regulated in CD4(+) and CD8(+) T cells from the PT group after stimulation with all peptides. Conclusions: The peptide epitopes can differentially stimulate cells from SC, AD, and PT individuals, leading to distinct immune responses. Frontiers Media S.A. 2020-02-14 /pmc/articles/PMC7033680/ /pubmed/32117204 http://dx.doi.org/10.3389/fimmu.2019.03145 Text en Copyright © 2020 e Silva, de Oliveira, da Silva, Brelaz de Castro, Ferreira, Hernandes, de Brito, de-Melo-Neto, Rezende and Pereira. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology e Silva, Rafael de Freitas de Oliveira, Beatriz Coutinho da Silva, Ailton Alvaro Brelaz de Castro, Maria Carolina Accioly Ferreira, Luiz Felipe Gomes Rebello Hernandes, Marcelo Zaldini de Brito, Maria Edileuza Felinto de-Melo-Neto, Osvaldo Pompílio Rezende, Antônio Mauro Pereira, Valéria Rêgo Alves Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis |
title | Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis |
title_full | Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis |
title_fullStr | Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis |
title_full_unstemmed | Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis |
title_short | Immunogenicity of Potential CD4(+) and CD8(+) T Cell Epitopes Derived From the Proteome of Leishmania braziliensis |
title_sort | immunogenicity of potential cd4(+) and cd8(+) t cell epitopes derived from the proteome of leishmania braziliensis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033680/ https://www.ncbi.nlm.nih.gov/pubmed/32117204 http://dx.doi.org/10.3389/fimmu.2019.03145 |
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