Identification of conserved and HLA promiscuous DENV3 T-cell epitopes.
Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand...
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ftdoajarticles:oai:doaj.org/article:f24c1ad27b214fe28a6d141085c063f7 2023-05-15T15:11:31+02:00 Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. Eduardo J M Nascimento Robbie B Mailliard Asif M Khan John Sidney Alessandro Sette Nicole Guzman Michael Paulaitis Andréa Barbosa de Melo Marli T Cordeiro Laura V G Gil Françoir Lemonnier Charles Rinaldo J Thomas August Ernesto T A Marques 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002497 https://doaj.org/article/f24c1ad27b214fe28a6d141085c063f7 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3794980?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002497 https://doaj.org/article/f24c1ad27b214fe28a6d141085c063f7 PLoS Neglected Tropical Diseases, Vol 7, Iss 10, p e2497 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002497 2022-12-30T21:58:07Z Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 10 e2497 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Eduardo J M Nascimento Robbie B Mailliard Asif M Khan John Sidney Alessandro Sette Nicole Guzman Michael Paulaitis Andréa Barbosa de Melo Marli T Cordeiro Laura V G Gil Françoir Lemonnier Charles Rinaldo J Thomas August Ernesto T A Marques Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design. |
format |
Article in Journal/Newspaper |
author |
Eduardo J M Nascimento Robbie B Mailliard Asif M Khan John Sidney Alessandro Sette Nicole Guzman Michael Paulaitis Andréa Barbosa de Melo Marli T Cordeiro Laura V G Gil Françoir Lemonnier Charles Rinaldo J Thomas August Ernesto T A Marques |
author_facet |
Eduardo J M Nascimento Robbie B Mailliard Asif M Khan John Sidney Alessandro Sette Nicole Guzman Michael Paulaitis Andréa Barbosa de Melo Marli T Cordeiro Laura V G Gil Françoir Lemonnier Charles Rinaldo J Thomas August Ernesto T A Marques |
author_sort |
Eduardo J M Nascimento |
title |
Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
title_short |
Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
title_full |
Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
title_fullStr |
Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
title_full_unstemmed |
Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
title_sort |
identification of conserved and hla promiscuous denv3 t-cell epitopes. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002497 https://doaj.org/article/f24c1ad27b214fe28a6d141085c063f7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 10, p e2497 (2013) |
op_relation |
http://europepmc.org/articles/PMC3794980?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002497 https://doaj.org/article/f24c1ad27b214fe28a6d141085c063f7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002497 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
10 |
container_start_page |
e2497 |
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1766342357135917056 |