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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.03145/full |
| _version_ | 1819208386046066688 |
|---|---|
| author | Rafael de Freitas e Silva Rafael de Freitas e Silva Beatriz Coutinho de Oliveira Ailton Alvaro da Silva Maria Carolina Accioly Brelaz de Castro Maria Carolina Accioly Brelaz de Castro Luiz Felipe Gomes Rebello Ferreira Marcelo Zaldini Hernandes Maria Edileuza Felinto de Brito Osvaldo Pompílio de-Melo-Neto Antônio Mauro Rezende Valéria Rêgo Alves Pereira |
| author_facet | Rafael de Freitas e Silva Rafael de Freitas e Silva Beatriz Coutinho de Oliveira Ailton Alvaro da Silva Maria Carolina Accioly Brelaz de Castro Maria Carolina Accioly Brelaz de Castro Luiz Felipe Gomes Rebello Ferreira Marcelo Zaldini Hernandes Maria Edileuza Felinto de Brito Osvaldo Pompílio de-Melo-Neto Antônio Mauro Rezende Valéria Rêgo Alves Pereira |
| author_sort | Rafael de Freitas e Silva |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T05:38:33Z |
| format | Article |
| id | doaj.art-839b768bcf44497d8cfd017d62dc449c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T05:38:33Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-839b768bcf44497d8cfd017d62dc449c2022-12-21T17:58:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011010.3389/fimmu.2019.03145469814Immunogenicity of Potential CD4+ and CD8+ T Cell Epitopes Derived From the Proteome of Leishmania braziliensisRafael de Freitas e Silva0Rafael de Freitas e Silva1Beatriz Coutinho de Oliveira2Ailton Alvaro da Silva3Maria Carolina Accioly Brelaz de Castro4Maria Carolina Accioly Brelaz de Castro5Luiz Felipe Gomes Rebello Ferreira6Marcelo Zaldini Hernandes7Maria Edileuza Felinto de Brito8Osvaldo Pompílio de-Melo-Neto9Antônio Mauro Rezende10Valéria Rêgo Alves Pereira11Department of Natural Sciences, Universidade de Pernambuco, Garanhuns, BrazilDepartment of Immunology, Fundação Oswaldo Cruz, Recife, BrazilDepartment of Immunology, Fundação Oswaldo Cruz, Recife, BrazilDepartment of Immunology, Fundação Oswaldo Cruz, Recife, BrazilDepartment of Immunology, Fundação Oswaldo Cruz, Recife, BrazilParasitology Laboratory, Universidade Federal de Pernambuco, Vitória de Santo Antão, BrazilDepartment of Pharmaceutical Sciences, Universidade Federal de Pernambuco, Recife, BrazilDepartment of Pharmaceutical Sciences, Universidade Federal de Pernambuco, Recife, BrazilDepartment of Immunology, Fundação Oswaldo Cruz, Recife, BrazilDepartment of Microbiology, Fundação Oswaldo Cruz, Recife, BrazilDepartment of Microbiology, Fundação Oswaldo Cruz, Recife, BrazilDepartment of Immunology, Fundação Oswaldo Cruz, Recife, BrazilBackground: 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.03145/fullneglected diseasescutaneous leishmaniasisLeishmania (Viannia) braziliensisimmunogenicityCD4+ CD8+ T cell epitopes |
| spellingShingle | Rafael de Freitas e Silva Rafael de Freitas e Silva Beatriz Coutinho de Oliveira Ailton Alvaro da Silva Maria Carolina Accioly Brelaz de Castro Maria Carolina Accioly Brelaz de Castro Luiz Felipe Gomes Rebello Ferreira Marcelo Zaldini Hernandes Maria Edileuza Felinto de Brito Osvaldo Pompílio de-Melo-Neto Antônio Mauro Rezende Valéria Rêgo Alves Pereira Immunogenicity of Potential CD4+ and CD8+ T Cell Epitopes Derived From the Proteome of Leishmania braziliensis Frontiers in Immunology neglected diseases cutaneous leishmaniasis Leishmania (Viannia) braziliensis immunogenicity CD4+ CD8+ T cell epitopes |
| 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 | neglected diseases cutaneous leishmaniasis Leishmania (Viannia) braziliensis immunogenicity CD4+ CD8+ T cell epitopes |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.03145/full |
| work_keys_str_mv | AT rafaeldefreitasesilva immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT rafaeldefreitasesilva immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT beatrizcoutinhodeoliveira immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT ailtonalvarodasilva immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT mariacarolinaacciolybrelazdecastro immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT mariacarolinaacciolybrelazdecastro immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT luizfelipegomesrebelloferreira immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT marcelozaldinihernandes immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT mariaedileuzafelintodebrito immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT osvaldopompiliodemeloneto immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT antoniomaurorezende immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis AT valeriaregoalvespereira immunogenicityofpotentialcd4andcd8tcellepitopesderivedfromtheproteomeofleishmaniabraziliensis |