title: Narrowed TCR diversity for immunised mice challenged with recombinant influenza A-HIV Env(311-320) virus.
abstract: Understanding CD8+ T cell responses generated by live virus vectors is critical for the rational design of next generation HIV CTL-based vaccines. We used recombinant influenza viruses expressing the HIV Env(311-320) peptide in the neuraminidase stalk to study response magnitude, cytokine production and repertoire diversity for the elicited CD8+ D(d)Env(311) CTL set. The insertion of the CD8+ D(d)Env(311) epitope into the NA stalk resulted in a decrease in viral fitness that was reflected in lower lung viral titres. While not affecting the magnitude of endogenous primary influenza-specific responses, the introduction of the D(d)Env(311) CD8+ T cell epitope altered the hierarchy of responses following secondary challenge. The CD8+ K(d)NP(147) response increased 9-fold in the spleen following secondary infection whereas the CD8+ D(d)Env(311) response increased 15-fold in the spleen. Moreover, this study is the first to describe narrowing of CD8+ TCR repertoire diversity in the context of an evolving secondary immune response against influenza A virus. Analysis of Vbeta bias for CD8+ D(d)Env(311) T cell responses showed a narrowing of CD8+ Vbeta8.1/8.2 D(d)Env(311) TCR repertoire diversity. This work further emphasizes the importance of understanding vaccine-induced CD8+ T cell responses.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
authors.forename: Tania
authors.initials: T
authors.lastname: Cukalac
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Moffat
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: John
authors.initials: J
authors.lastname: Stambas
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000502:physiology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; D009439:Neuraminidase