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: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2010
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/febb3b7cf5ee448a93bdacd39aead574 |
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| Sumario: | <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 DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 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. |
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