@article{43e62440779611df928f000ea68e967b,
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}",
year = "2010",
month = jan,
day = "1",
doi = "10.1371/journal.pone.0010533",
language = "English",
volume = "5",
pages = "e10533",
journal = "PLoS Computational Biology",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",
}
