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Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes

Nascimento, EJM and Mailliard, RB and Khan, AM and Sidney, J and Sette, A and Guzman, N and Paulaitis, M and de Melo, AB and Cordeiro, MT and Gil, LVG and Lemonnier, F and Rinaldo, C and August, JT and Marques, ETA (2013) Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes. PLoS Neglected Tropical Diseases, 7 (10). ISSN 1935-2727

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Abstract

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. © 2013 Nascimento et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nascimento, EJMejmn@pitt.eduEJMN
Mailliard, RBrbm19@pitt.eduRBM190000-0001-5501-503X
Khan, AM
Sidney, J
Sette, A
Guzman, N
Paulaitis, M
de Melo, AB
Cordeiro, MT
Gil, LVG
Lemonnier, F
Rinaldo, CRINALDO@pitt.eduRINALDO
August, JT
Marques, ETAmarques@pitt.eduMARQUES
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHarris, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Center for Vaccine Research
Date: 1 January 2013
Date Type: Publication
Journal or Publication Title: PLoS Neglected Tropical Diseases
Volume: 7
Number: 10
DOI or Unique Handle: 10.1371/journal.pntd.0002497
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
ISSN: 1935-2727
Date Deposited: 02 Jul 2014 21:32
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/22191

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