PMID- 22039500
OWN - NLM
STAT- MEDLINE
DCOM- 20120228
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 10
DP  - 2011
TI  - Human leukocyte antigen (HLA) class I restricted epitope discovery in yellow 
      fewer and dengue viruses: importance of HLA binding strength.
PG  - e26494
LID - 10.1371/journal.pone.0026494 [doi]
LID - e26494
AB  - Epitopes from all available full-length sequences of yellow fever virus (YFV) and 
      dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) 
      alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A 
      subset of 179 predicted YFV and 158 predicted DENV epitopes were selected using 
      the EpiSelect algorithm to allow for optimal coverage of viral strains. The 
      selected predicted epitopes were synthesized and approximately 75% were found to 
      bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 
      500 nM. The immunogenicity of 25 HLA-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 
      binding peptides was tested in three HLA-transgenic mice models and led to the 
      identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic 
      peptides. The immunogenic peptides bound HLA significantly stronger than the 
      non-immunogenic peptides. All except one of the immunogenic peptides had K(D) 
      below 100 nM and the peptides with K(D) below 5 nM were more likely to be 
      immunogenic. In addition, all the immunogenic peptides that were identified as 
      having a high functional avidity had K(D) below 20 nM. A*02:01 transgenic mice 
      were also inoculated twice with the 17DD YFV vaccine strain. Three of the YFV 
      A*02:01 restricted peptides activated T-cells from the infected mice in vitro. 
      All three peptides that elicited responses had an HLA binding affinity of 2 nM or 
      less. The results indicate the importance of the strength of HLA binding in 
      shaping the immune response.
FAU - Lund, Ole
AU  - Lund O
AD  - Department of Systems Biology, Center for Biological Sequence Analysis, Technical 
      University of Denmark, Lyngby, Denmark. lund@cbs.dtu.dk
FAU - Nascimento, Eduardo J M
AU  - Nascimento EJ
FAU - Maciel, Milton Jr
AU  - Maciel M Jr
FAU - Nielsen, Morten
AU  - Nielsen M
FAU - Larsen, Mette Voldby
AU  - Larsen MV
FAU - Lundegaard, Claus
AU  - Lundegaard C
FAU - Harndahl, Mikkel
AU  - Harndahl M
FAU - Lamberth, Kasper
AU  - Lamberth K
FAU - Buus, Soren
AU  - Buus S
FAU - Salmon, Jerome
AU  - Salmon J
FAU - August, Thomas J
AU  - August TJ
FAU - Marques, Ernesto T A Jr
AU  - Marques ET Jr
LA  - eng
GR  - HHSN266200400025C/PHS HHS/United States
GR  - HHSN266200400083C/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111019
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Yellow Fever Vaccine)
SB  - IM
EIN - PLoS One. 2011;6(11). doi:10.1371/annotation/254c9f39-1c6b-4f48-a947-b4ed931642e7
MH  - Amino Acid Sequence
MH  - Animals
MH  - Dengue Virus/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes/chemistry/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Yellow Fever Vaccine/immunology
MH  - Yellow fever virus/*immunology
PMC - PMC3198402
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/11/01 06:00
MHDA- 2012/03/01 06:00
PMCR- 2011/10/19
CRDT- 2011/11/01 06:00
PHST- 2011/05/31 00:00 [received]
PHST- 2011/09/28 00:00 [accepted]
PHST- 2011/11/01 06:00 [entrez]
PHST- 2011/11/01 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
PHST- 2011/10/19 00:00 [pmc-release]
AID - PONE-D-11-09759 [pii]
AID - 10.1371/journal.pone.0026494 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(10):e26494. doi: 10.1371/journal.pone.0026494. Epub 2011 Oct 19.