HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses

Publication: Research - peer-reviewJournal article – Annual report year: 2010

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HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses. / Wang, M. J.; Larsen, Mette Voldby; Nielsen, Morten; Harndahl, M.; Justesen, S.; Dziegiel, M.H.; Buus, S.; Tang, Sheila Tuyet; Lund, Ole; Claesson, M.H.

In: P L o S One, Vol. 5, No. 5, 2010, p. e10533.

Publication: Research - peer-reviewJournal article – Annual report year: 2010

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APA

Wang, M. J., Larsen, M. V., Nielsen, M., Harndahl, M., Justesen, S., Dziegiel, M. H., ... Claesson, M. H. (2010). HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses. P L o S One, 5(5), e10533. 10.1371/journal.pone.0010533

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Author

Wang, M. J.; Larsen, Mette Voldby; Nielsen, Morten; Harndahl, M.; Justesen, S.; Dziegiel, M.H.; Buus, S.; Tang, Sheila Tuyet; Lund, Ole; Claesson, M.H. / HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses.

In: P L o S One, Vol. 5, No. 5, 2010, p. e10533.

Publication: Research - peer-reviewJournal article – Annual report year: 2010

Bibtex

@article{7e4e2d2480414d8fbf5eafa2d4876fd5,
title = "HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses",
publisher = "Public Library of Science",
author = "Wang, {M. J.} and Larsen, {Mette Voldby} and Morten Nielsen and M. Harndahl and S. Justesen and M.H. Dziegiel and S. Buus and Tang, {Sheila Tuyet} and Ole Lund and M.H. Claesson",
note = "This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2010",
doi = "10.1371/journal.pone.0010533",
volume = "5",
number = "5",
pages = "e10533",
journal = "P L o S One",
issn = "1932-6203",

}

RIS

TY - JOUR

T1 - HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses

A1 - Wang,M. J.

A1 - Larsen,Mette Voldby

A1 - Nielsen,Morten

A1 - Harndahl,M.

A1 - Justesen,S.

A1 - Dziegiel,M.H.

A1 - Buus,S.

A1 - Tang,Sheila Tuyet

A1 - Lund,Ole

A1 - Claesson,M.H.

AU - Wang,M. J.

AU - Larsen,Mette Voldby

AU - Nielsen,Morten

AU - Harndahl,M.

AU - Justesen,S.

AU - Dziegiel,M.H.

AU - Buus,S.

AU - Tang,Sheila Tuyet

AU - Lund,Ole

AU - Claesson,M.H.

PB - Public Library of Science

PY - 2010

Y1 - 2010

N2 - 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 IFN gamma 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.

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 IFN gamma 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.

U2 - 10.1371/journal.pone.0010533

DO - 10.1371/journal.pone.0010533

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 5

VL - 5

SP - e10533

ER -