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Immunology. 2016 Feb;147(2):165-77. doi: 10.1111/imm.12548. Epub 2015 Dec 8.

Epitope specific T-cell responses against influenza A in a healthy population.

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  • 1Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
  • 2K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.
  • 3La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
  • 4The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.


Pre-existing human CD4(+) and CD8(+) T-cell-mediated immunity may be a useful correlate of protection against severe influenza disease. Identification and evaluation of common epitopes recognized by T cells with broad cross-reactivity is therefore important to guide universal influenza vaccine development, and to monitor immunological preparedness against pandemics. We have retrieved an optimal combination of MHC class I and class II restricted epitopes from the Immune Epitope Database (, by defining a fitness score function depending on prevalence, sequence conservancy and HLA super-type coverage. Optimized libraries of CD4(+) and CD8(+) T-cell epitopes were selected from influenza antigens commonly present in seasonal and pandemic influenza strains from 1934 to 2009. These epitope pools were used to characterize human T-cell responses in healthy donors using interferon-γ ELISPOT assays. Upon stimulation, significant CD4(+) and CD8(+) T-cell responses were induced, primarily recognizing epitopes from the conserved viral core proteins. Furthermore, the CD4(+) and CD8(+) T cells were phenotypically characterized regarding functionality, cytotoxic potential and memory phenotype using flow cytometry. Optimized sets of T-cell peptide epitopes may be a useful tool to monitor the efficacy of clinical trials, the immune status of a population to predict immunological preparedness against pandemics, as well as being candidates for universal influenza vaccines.


T-cell epitopes; biomarkers; cross-reactivity; influenza A virus; vaccine

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