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Title: HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses
Type: Journal articleJournal article
Participant(s):
Forfatter:  Wang, M. J.
Technical University of Denmark

Author:  Larsen, Mette Voldby (Cwisno: 24381)
Technical University of Denmark
Email:

Author:  Nielsen, Morten (Cwisno: 5973)
Technical University of Denmark
Email:

Forfatter:  Harndahl, M.
Technical University of Denmark

Forfatter:  Justesen, S.
Technical University of Denmark

Forfatter:  Dziegiel, M.H.
Technical University of Denmark

Forfatter:  Buus, S.
Technical University of Denmark

Author:  Tang, Sheila Tuyet (Cwisno: 29428)
Technical University of Denmark

Author:  Lund, Ole (Cwisno: 5094)
Technical University of Denmark
Email:

Forfatter:  Claesson, M.H.
Technical University of Denmark
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 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.
Published: in journal: P L o S One (ISSN: 1932-6203) (DOI: http://dx.doi.org/10.1371/journal.pone.0010533), vol: 5, issue: 5, pages: e10533, 2010
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