title: Overcoming original antigenic sin to generate new CD8 T cell IFN-gamma responses in an antigen-experienced host.
abstract: The failure to mount effective immunity to virus variants in a previously virus-infected host is known as original antigenic sin. We have previously shown that prior immunity to a virus capsid protein inhibits induction by immunization of an IFN-gamma CD8+ T cell response to an epitope linked to the capsid protein. We now demonstrate that capsid protein-primed CD4+ T cells secrete IL-10 in response to capsid protein presented by dendritic cells, and deviate CD8+ T cells responding to a linked MHC class I-restricted epitope to reduce IFN-gamma production. Neutralizing IL-10 while delivering further linked epitope, either in vitro or in vivo, restores induction by immunization of an Ag-specific IFN-gamma response to the epitope. This finding demonstrates a strategy for overcoming inhibition of MHC class I epitopes upon immunization of a host already primed to Ag, which may facilitate immunotherapy for chronic viral infection or cancer.
authors.affiliation: Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, Australia. xliu@cicr.uq.edu.au
authors.forename: Xiao Song
authors.initials: XS
authors.lastname: Liu
authors.forename: Joanne
authors.initials: J
authors.lastname: Dyer
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.forename: Jie
authors.initials: J
authors.lastname: Zhong
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2 / Q000276:immunology; D018411:Spodoptera
chemical_list: C423449:CpG ODN 1826; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2; C059731:oncogene protein E7, Human papillomavirus type 16; D016753:Interleukin-10; D007371:Interferon-gamma; D004247:DNA