title: Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.
abstract: Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 "Spanish flu" rather than more recent "seasonal" strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.
authors.affiliation: Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Valkenburg
authors.forename: Karen
authors.initials: K
authors.lastname: Laurie
authors.forename: Yu Chih
authors.initials: YC
authors.lastname: Liu
authors.forename: Justin T
authors.initials: JT
authors.lastname: Denholm
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Richards
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection; D003429:Cross Reactions / Q000276:immunology; D004196:Disease Outbreaks; D000939:Epitopes / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D018655:Lymphocyte Count; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014780:Viruses / Q000276:immunology
chemical_list: D000939:Epitopes; D015235:HLA-B Antigens; D007252:Influenza Vaccines