title: CD4+ T cells recognize unique and conserved 2009 H1N1 influenza hemagglutinin epitopes after natural infection and vaccination.
abstract: Influenza A/California/4/2009 (H1N1/09) is a recently emerged influenza virus capable of causing serious illness or death in otherwise healthy individuals. Serious outcomes were most common in young adults and children, suggesting that pre-existing heterologous immunity may influence the severity of infection. Using tetramers, we identified CD4(+) T-cell epitopes within H1N1/09 hemagglutinin (HA) that share extensive homology with seasonal influenza and epitopes that are unique to H1N1/09 HA. Ex vivo tetramer staining revealed that T cells specific for conserved epitopes were detectable within the memory compartment, whereas T cells specific for unique epitopes were naive and infrequent prior to infection or vaccination. Following infection, the frequencies of T cells specific for unique epitopes were 11-fold higher, reaching levels comparable to those of T cells specific for immunodominant epitopes. In contrast, the frequencies of T cells specific for conserved epitopes were only 2- to 3-fold higher following infection. In general, H1HA-reactive T cells exhibited a memory phenotype, expressed CXCR3 and secreted IFN-γ, indicating a predominantly Th1-polarized response. A similar Th1 response was seen in vaccinated subjects, but the expansion of T cells specific for HA epitopes was comparatively modest after vaccination. Our findings indicate that CD4(+) T cells recognize both strain-specific and conserved epitopes within the influenza HA protein and suggest that naive T cells specific for HA epitopes undergo significant expansion, whereas memory T cells specific for the conserved epitopes undergo more restrained expansion.
authors.affiliation: Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA 98101, USA.
authors.forename: Junbao
authors.initials: J
authors.lastname: Yang
authors.forename: Eddie
authors.initials: E
authors.lastname: James
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Gates
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: DeLong
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: LaFond
authors.forename: Uma
authors.initials: U
authors.lastname: Malhotra
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology*; D008875:Middle Aged; D014611:Vaccination
chemical_list: D000939:Epitopes; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: HLA; ex vivo; naive; peptide; tetramer