In contrast to the current antibody-mediated and strain-specific influenza vaccines, T-cells directed at conserved internal proteins elicit broad immunity against seasonal and pandemic influenza viruses. Here, we dissected the optimal human influenza-specific CD8+ T-cell populations across different HLAs, both at functional and clonal levels, to provide insights into universal immunity against influenza. We found that although sporadic variations can be found across many peptides, mutations ‘escaping’ T-cell recognition get fixed only for selected CD8+ T-cell populations. Using a human single-cell multiplex RT-PCR for TCRαβ, we found that specific TCRs can recognize multiple variants derived from different influenza strains. For example, a dominant public TCR clone found at high frequency within M158+CD8+ T-cell responses in all HLA-A*0201+ individuals can recognize the naturally-occurring variants of the peptide. This suggests that the globally common HLA-A2+ population have universal T-cell immunity to any M158 variant, which can, at least in part, explain high conservation level for M158. In addition, our current analyses across other HLAs including HLA-A*01, greatly extend these findings. Our study provides insights into the diversity of the CD8 T cell response against influenza and may help unravel beneficial targets needed for a successful universal vaccine against both season and pandemic influenza strains.
- Copyright © 2013 by The American Association of Immunologists, Inc.