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, Thomas August, Ernesto T A Marques

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere2497
JournalPLoS Neglected Tropical Diseases
Volume7
Issue number10
DOIs
StatePublished - Oct 2013

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Dengue Virus
T-Lymphocyte Epitopes
HLA Antigens
Dengue
Epitopes
T-Lymphocytes
Transgenic Mice
varespladib methyl
Peptides
Peptide T
Serogroup
Enzyme-Linked Immunospot Assay
Conserved Sequence
Volunteers
Immunity
Vaccines
Immunoglobulin G
Ligands

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Nascimento, E. J. M., Mailliard, R. B., Khan, A. M., Sidney, J., Sette, A., Guzman, N., ... Marques, E. T. A. (2013). Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes. PLoS Neglected Tropical Diseases, 7(10), [e2497]. https://doi.org/10.1371/journal.pntd.0002497

Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes. / Nascimento, Eduardo J M; Mailliard, Robbie B.; Khan, Asif M.; Sidney, John; Sette, Alessandro; Guzman, Nicole; Paulaitis, Michael; de Melo, Andréa Barbosa; Cordeiro, Marli T.; Gil, Laura V G; Lemonnier, Françoir; Rinaldo, Charles; August, Thomas; Marques, Ernesto T A.

In: PLoS Neglected Tropical Diseases, Vol. 7, No. 10, e2497, 10.2013.

Research output: Contribution to journalArticle

Nascimento, EJM, Mailliard, RB, Khan, AM, Sidney, J, Sette, A, Guzman, N, Paulaitis, M, de Melo, AB, Cordeiro, MT, Gil, LVG, Lemonnier, F, Rinaldo, C, August, T & Marques, ETA 2013, 'Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes', PLoS Neglected Tropical Diseases, vol. 7, no. 10, e2497. https://doi.org/10.1371/journal.pntd.0002497
Nascimento EJM, Mailliard RB, Khan AM, Sidney J, Sette A, Guzman N et al. Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes. PLoS Neglected Tropical Diseases. 2013 Oct;7(10). e2497. https://doi.org/10.1371/journal.pntd.0002497
Nascimento, Eduardo J M ; Mailliard, Robbie B. ; Khan, Asif M. ; Sidney, John ; Sette, Alessandro ; Guzman, Nicole ; Paulaitis, Michael ; de Melo, Andréa Barbosa ; Cordeiro, Marli T. ; Gil, Laura V G ; Lemonnier, Françoir ; Rinaldo, Charles ; August, Thomas ; Marques, Ernesto T A. / Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes. In: PLoS Neglected Tropical Diseases. 2013 ; Vol. 7, No. 10.
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