PMID- 20479886
OWN - NLM
STAT- MEDLINE
DCOM- 20100907
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 5
DP  - 2010 May 7
TI  - HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell 
      responses.
PG  - e10533
LID - 10.1371/journal.pone.0010533 [doi]
LID - e10533
AB  - BACKGROUND: Identification of human leukocyte antigen class I (HLA-I) restricted 
      cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the 
      development of new effective peptide-based vaccines. METHODOLOGY/PRINCIPAL 
      FINDINGS: In the present work, bioinformatics was used to predict 9mer peptides 
      derived from available influenza A viral proteins with binding affinity for at 
      least one of the 12 HLA-I supertypes. The predicted peptides were then selected 
      in a way that ensured maximal coverage of the available influenza A strains. One 
      hundred and thirty one peptides were synthesized and their binding affinities for 
      the HLA-I supertypes were measured in a biochemical assay. Influenza-specific T 
      cell responses towards the peptides were quantified using IFNgamma ELISPOT assays 
      with peripheral blood mononuclear cells (PBMC) from adult healthy HLA-I typed 
      donors as responder cells. Of the 131 peptides, 21 were found to induce T cell 
      responses in 19 donors. In the ELISPOT assay, five peptides induced responses 
      that could be totally blocked by the pan-specific anti-HLA-I antibody W6/32, 
      whereas 15 peptides induced responses that could be completely blocked in the 
      presence of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking 
      of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked 
      by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC 
      depleted of CD4(+) or CD8(+) T cells prior to the ELISPOT culture revealed that 
      effectors are either CD4(+) (the majority of reactivities) or CD8(+) T cells, 
      never a mixture of these subsets. Three of the peptides, recognized by CD4(+) T 
      cells showed binding to recombinant DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 
      molecules in a recently developed biochemical assay. CONCLUSIONS/SIGNIFICANCE: 
      HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4(+) T 
      cell responses restricted by HLA-II molecules.
FAU - Wang, Mingjun
AU  - Wang M
AD  - Department of International Health, Immunology and Microbiology, Faculty of Heath 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Larsen, Mette V
AU  - Larsen MV
FAU - Nielsen, Morten
AU  - Nielsen M
FAU - Harndahl, Mikkel
AU  - Harndahl M
FAU - Justesen, Sune
AU  - Justesen S
FAU - Dziegiel, Morten H
AU  - Dziegiel MH
FAU - Buus, Soren
AU  - Buus S
FAU - Tang, Sheila T
AU  - Tang ST
FAU - Lund, Ole
AU  - Lund O
FAU - Claesson, Mogens H
AU  - Claesson MH
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100507
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Epitopes)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Blocking/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology/*virology
MH  - CD8-Positive T-Lymphocytes/immunology/virology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes/immunology
MH  - HLA-DR Antigens/immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Histocompatibility Antigens Class II/genetics/immunology
MH  - Humans
MH  - Influenza A virus/*immunology
MH  - Interferon-gamma/immunology
MH  - Lymphocyte Depletion
MH  - Middle Aged
MH  - Peptides/*immunology
MH  - Protein Binding/immunology
MH  - Reproducibility of Results
MH  - T-Lymphocytes, Cytotoxic/immunology/virology
MH  - Tissue Donors
PMC - PMC2866539
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/05/19 06:00
MHDA- 2010/09/08 06:00
PMCR- 2010/05/07
CRDT- 2010/05/19 06:00
PHST- 2010/03/01 00:00 [received]
PHST- 2010/04/16 00:00 [accepted]
PHST- 2010/05/19 06:00 [entrez]
PHST- 2010/05/19 06:00 [pubmed]
PHST- 2010/09/08 06:00 [medline]
PHST- 2010/05/07 00:00 [pmc-release]
AID - 10-PONE-RA-16714R1 [pii]
AID - 10.1371/journal.pone.0010533 [doi]
PST - epublish
SO  - PLoS One. 2010 May 7;5(5):e10533. doi: 10.1371/journal.pone.0010533.