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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC3794980?pdf=render |
| _version_ | 1811266620479242240 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T20:46:32Z |
| format | Article |
| id | doaj.art-f24c1ad27b214fe28a6d141085c063f7 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-04-12T20:46:32Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-f24c1ad27b214fe28a6d141085c063f72022-12-22T03:17:16ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352013-01-01710e249710.1371/journal.pntd.0002497Identification of conserved and HLA promiscuous DENV3 T-cell epitopes.Eduardo J M NascimentoRobbie B MailliardAsif M KhanJohn SidneyAlessandro SetteNicole GuzmanMichael PaulaitisAndréa Barbosa de MeloMarli T CordeiroLaura V G GilFrançoir LemonnierCharles RinaldoJ Thomas AugustErnesto T A MarquesAnti-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.http://europepmc.org/articles/PMC3794980?pdf=render |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| title | 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_short | Identification of conserved and HLA promiscuous DENV3 T-cell epitopes. |
| title_sort | identification of conserved and hla promiscuous denv3 t cell epitopes |
| url | http://europepmc.org/articles/PMC3794980?pdf=render |
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