title: 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.
abstract: 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 HA2113-131from 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.
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg.
authors.forename: I-Na
authors.initials: IN
authors.lastname: Lu
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg.
authors.forename: Sophie
authors.initials: S
authors.lastname: Farinelle
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Sausy
authors.affiliation: Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg.
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D058873:Pandemics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D059467:Transcriptome
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011948:Receptors, Antigen, T-Cell; C483468:hemagglutinin, human influenza A virus