The context of epitope presentation can influence functional quality of recalled influenza A virus-specific memory CD8+ T cells.
Lipopeptide constructs offer a novel strategy for eliciting effective cellular and humoral immunity by directly targeting the vaccine Ag to dendritic cells. Importantly, it is not known how closely immunity generated after lipopeptide vaccination mimics that generated after natural infection. We have used a novel lipopeptide vaccine strategy to analyze both the quantity and quality of CD8(+) T cell immunity to an influenza A virus epitope derived from the acidic polymerase protein (PA(224)) in B6 mice. Vaccination with the PA(224) lipopeptide resulted in accelerated viral clearance after subsequent influenza virus infection. The lipopeptide was also effective at recalling secondary D(b)PA(224) responses in the lung. Lipopeptide recalled D(b)PA(224)-specific CTL produced lower levels of IFN-gamma and TNF-alpha, but produced similar levels of IL-2 when compared with D(b)PA(224)-specific CTL recalled after virus infection. Furthermore, lipopeptide- and virus-recalled CTL demonstrated similar TCR avidity. Interestingly, lipopeptide administration resulted in expansion of D(b)PA(224)-specific CTL using a normally subdominant TCRBV gene segment. Overall, these results demonstrate that protective CTL responses elicited by lipopeptide vaccines can be correlated with TCR avidity, IL-2 production, and broad TCR repertoire diversity. Furthermore, factors that impact the quality of immunity are discussed. These factors are important considerations when evaluating the efficacy of novel vaccine strategies that target dendritic cells for eliciting cellular immunity.
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
E Bridie
EB
Day
Weiguang
W
Zeng
Peter C
PC
Doherty
David C
DC
Jackson
Katherine
K
Kedzierska
Stephen J
SJ
Turner
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology* / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D012324:RNA-Dependent RNA Polymerase / Q000276:immunology* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination; D014764:Viral Proteins / Q000276:immunology* / Q000494:pharmacology
D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines; D007376:Interleukin-2; D008074:Lipoproteins; C061290:PA protein, influenza viruses; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D007371:Interferon-gamma; D012324:RNA-Dependent RNA Polymerase