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

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>In the present work...

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Autores principales:	Mingjun Wang, Mette V Larsen, Morten Nielsen, Mikkel Harndahl, Sune Justesen, Morten H Dziegiel, Søren Buus, Sheila T Tang, Ole Lund, Mogens H Claesson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/febb3b7cf5ee448a93bdacd39aead574
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spelling	oai:doaj.org-article:febb3b7cf5ee448a93bdacd39aead5742021-12-02T20:21:49ZHLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.1932-620310.1371/journal.pone.0010533https://doaj.org/article/febb3b7cf5ee448a93bdacd39aead5742010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20479886/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 DRA10101/DRB10401 or DRA10101/DRB50101 molecules in a recently developed biochemical assay.<h4>Conclusions/significance</h4>HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4(+) T cell responses restricted by HLA-II molecules.Mingjun WangMette V LarsenMorten NielsenMikkel HarndahlSune JustesenMorten H DziegielSøren BuusSheila T TangOle LundMogens H ClaessonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10533 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mingjun Wang Mette V Larsen Morten Nielsen Mikkel Harndahl Sune Justesen Morten H Dziegiel Søren Buus Sheila T Tang Ole Lund Mogens H Claesson HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 DRA10101/DRB10401 or DRA10101/DRB50101 molecules in a recently developed biochemical assay.<h4>Conclusions/significance</h4>HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4(+) T cell responses restricted by HLA-II molecules.
format	article
author	Mingjun Wang Mette V Larsen Morten Nielsen Mikkel Harndahl Sune Justesen Morten H Dziegiel Søren Buus Sheila T Tang Ole Lund Mogens H Claesson
author_facet	Mingjun Wang Mette V Larsen Morten Nielsen Mikkel Harndahl Sune Justesen Morten H Dziegiel Søren Buus Sheila T Tang Ole Lund Mogens H Claesson
author_sort	Mingjun Wang
title	HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
title_short	HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
title_full	HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
title_fullStr	HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
title_full_unstemmed	HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
title_sort	hla class i binding 9mer peptides from influenza a virus induce cd4 t cell responses.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/febb3b7cf5ee448a93bdacd39aead574
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HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.

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