PMID- 24130917
OWN - NLM
STAT- MEDLINE
DCOM- 20140505
LR  - 20211021
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 7
IP  - 10
DP  - 2013
TI  - Identification of conserved and HLA promiscuous DENV3 T-cell epitopes.
PG  - e2497
LID - 10.1371/journal.pntd.0002497 [doi]
LID - e2497
AB  - 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 naive 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.
FAU - Nascimento, Eduardo J M
AU  - Nascimento EJ
AD  - Department of Infectious Disease and Microbiology, University of Pittsburgh, 
      Pittsburgh, Pennsylvania, United States of America ; Center for Vaccine Research, 
      University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
FAU - Mailliard, Robbie B
AU  - Mailliard RB
FAU - Khan, Asif M
AU  - Khan AM
FAU - Sidney, John
AU  - Sidney J
FAU - Sette, Alessandro
AU  - Sette A
FAU - Guzman, Nicole
AU  - Guzman N
FAU - Paulaitis, Michael
AU  - Paulaitis M
FAU - de Melo, Andrea Barbosa
AU  - de Melo AB
FAU - Cordeiro, Marli T
AU  - Cordeiro MT
FAU - Gil, Laura V G
AU  - Gil LV
FAU - Lemonnier, Francoir
AU  - Lemonnier F
FAU - Rinaldo, Charles
AU  - Rinaldo C
FAU - August, J Thomas
AU  - August JT
FAU - Marques, Ernesto T A Jr
AU  - Marques ET Jr
LA  - eng
GR  - HHSN272200900042C/AI/NIAID NIH HHS/United States
GR  - U19 AI056541/AI/NIAID NIH HHS/United States
GR  - U19 AI5654/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131010
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Antigens, Viral)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (La protein, human)
RN  - 0 (Phosphoproteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Antigens, Viral/*immunology
MH  - Child
MH  - Dengue Virus/*immunology
MH  - Enzyme-Linked Immunospot Assay
MH  - Epitope Mapping
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Phosphoproteins/*immunology/*metabolism
MH  - Protein Binding
PMC - PMC3794980
COIS- The authors have declared that no competing interests exist.
EDAT- 2013/10/17 06:00
MHDA- 2014/05/06 06:00
PMCR- 2013/10/10
CRDT- 2013/10/17 06:00
PHST- 2013/02/21 00:00 [received]
PHST- 2013/09/09 00:00 [accepted]
PHST- 2013/10/17 06:00 [entrez]
PHST- 2013/10/17 06:00 [pubmed]
PHST- 2014/05/06 06:00 [medline]
PHST- 2013/10/10 00:00 [pmc-release]
AID - PNTD-D-13-00285 [pii]
AID - 10.1371/journal.pntd.0002497 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2013 Oct 10;7(10):e2497. doi: 10.1371/journal.pntd.0002497. 
      eCollection 2013.