Journal article
HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4(+) T Cell Responses
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.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2010 |
Pages: | e10533 |
ISSN: | 19326203 , 15537358 and 1553734x |
Types: | Journal article |
DOI: | 10.1371/journal.pone.0010533 |
ORCIDs: | Nielsen, Morten , Lund, Ole , 0000-0001-8034-1523 and 0000-0001-8363-1999 |
Adult Aged Antibodies, Blocking CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Enzyme-Linked Immunosorbent Assay Epitopes HLA-DR Antigens Histocompatibility Antigens Class I Histocompatibility Antigens Class II Humans Influenza A virus Interferon-gamma Lymphocyte Depletion Medicine Middle Aged Peptides Protein Binding Q R Reproducibility of Results Science T-Lymphocytes, Cytotoxic Tissue Donors