Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice

摘要

The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain,which makes it a potential target for use as a universal vaccine against influenza.However,the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear.Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2113.131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza.In response to stimulation with the identified epitope,splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2,TNF-α and IFN-γ production as well as degranulation.Moreover,mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor β sequences,and they had a higher survival rate following a challenge with a lethal dose of pandemic H1N1 influenza virus.Thus,our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune response against influenza virus infection.