HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses

Mingjun Wang; Mette V Larsen; Morten Nielsen; Mikkel Harndahl; Sune Justesen; Morten H Dziegiel; Søren Buus; Sheila T Tang; Ole Lund; Mogens H Claesson; Mingjun Wang; Mette V Larsen; Morten Nielsen; Mikkel Nors Harndahl; Sune Justesen; Morten H Dziegiel; Søren Buus; Sheila Tuyet Tang; Ole Lund; Mogens Helweg Claesson

doi:10.1371/journal.pone.0010533

HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses

Mingjun Wang, Mette V Larsen, Morten Nielsen, Mikkel Harndahl, Sune Justesen, Morten H Dziegiel, Søren Buus, Sheila T Tang, Ole Lund, Mogens H Claesson, Mingjun Wang, Mette V Larsen, Morten Nielsen, Mikkel Nors Harndahl, Sune Justesen, Morten H Dziegiel, Søren Buus, Sheila Tuyet Tang, Ole Lund, Mogens Helweg Claesson

22 Citations (Scopus)

Abstract

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 IFNγ 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.

Original language	English
Journal	PLoS ONE
Volume	5
Issue number	5
Pages (from-to)	e10533
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0010533 https://doi.org/10.1371/journal.pone.0010533
Publication status	Published - 1 Jan 2010

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Wang, M., Larsen, M. V., Nielsen, M., Harndahl, M., Justesen, S., Dziegiel, M. H., Buus, S., Tang, S. T., Lund, O., Claesson, M. H., Wang, M., Larsen, M. V., Nielsen, M., Harndahl, M. N., Justesen, S., Dziegiel, M. H., Buus, S., Tang, S. T., Lund, O., & Claesson, M. H. (2010). HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses. PLoS ONE, 5(5), e10533. https://doi.org/10.1371/journal.pone.0010533, https://doi.org/10.1371/journal.pone.0010533

Wang, M, Larsen, MV, Nielsen, M, Harndahl, M, Justesen, S, Dziegiel, MH , Buus, S, Tang, ST, Lund, O, Claesson, MH, Wang, M, Larsen, MV, Nielsen, M, Harndahl, MN, Justesen, S, Dziegiel, MH, Buus, S, Tang, ST, Lund, O & Claesson, MH 2010, 'HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses', PLoS ONE, vol. 5, no. 5, pp. e10533. https://doi.org/10.1371/journal.pone.0010533, https://doi.org/10.1371/journal.pone.0010533

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title = "HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses",

abstract = "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 IFNγ 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.",

author = "Mingjun Wang and Larsen, {Mette V} and Morten Nielsen and Mikkel Harndahl and Sune Justesen and Dziegiel, {Morten H} and S{\o}ren Buus and Tang, {Sheila T} and Ole Lund and Claesson, {Mogens H} and Mingjun Wang and Larsen, {Mette V} and Morten Nielsen and Harndahl, {Mikkel Nors} and Sune Justesen and Dziegiel, {Morten H} and S{\o}ren Buus and Tang, {Sheila Tuyet} and Ole Lund and Claesson, {Mogens Helweg}",

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T1 - HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses

AU - Wang, Mingjun

AU - Larsen, Mette V

AU - Nielsen, Morten

AU - Harndahl, Mikkel

AU - Justesen, Sune

AU - Dziegiel, Morten H

AU - Buus, Søren

AU - Tang, Sheila T

AU - Lund, Ole

AU - Claesson, Mogens H

AU - Wang, Mingjun

AU - Larsen, Mette V

AU - Nielsen, Morten

AU - Harndahl, Mikkel Nors

AU - Justesen, Sune

AU - Dziegiel, Morten H

AU - Buus, Søren

AU - Tang, Sheila Tuyet

AU - Lund, Ole

AU - Claesson, Mogens Helweg

PY - 2010/1/1

Y1 - 2010/1/1

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 IFNγ 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 IFNγ 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

M3 - Journal article

C2 - 20479886

SN - 1932-6203

VL - 5

SP - e10533

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 5

ER -

HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses

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