title: Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.
abstract: CD8(+) T cells that recognize virus-derived peptides presented on MHC class I are vital antiviral effectors. Such peptides presented by any given virus vary greatly in immunogenicity, allowing them to be ranked in an immunodominance hierarchy. However, the full range of parameters that determine immunodominance and the underlying mechanisms remain unknown. In this study, we show across a range of vaccinia virus strains, including the current clonal smallpox vaccine, that the ability of a strain to spread systemically correlated with reduced immunodominance. Reduction in immunodominance was observed both in the lymphoid system and at the primary site of infection. Mechanistically, reduced immunodominance was associated with more robust priming and especially priming in the spleen. Finally, we show this is not just a property of vaccine and laboratory strains of virus, because an association between virulence and immunodominance was also observed in isolates from an outbreak of zoonotic vaccinia virus that occurred in Brazil.
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia;
authors.forename: Inge E A
authors.initials: IE
authors.lastname: Flesch
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia;
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Hollett
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia;
authors.forename: Yik Chun
authors.initials: YC
authors.lastname: Wong
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia; Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; and.
authors.forename: Bárbara Resende
authors.initials: BR
authors.lastname: Quinan
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Debbie
authors.initials: D
authors.lastname: Howard
authors.affiliation: Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; and.
authors.forename: Flávio G
authors.initials: FG
authors.lastname: da Fonseca
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia; John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia david.tscharke@anu.edu.au.
authors.forename: David C
authors.initials: DC
authors.lastname: Tscharke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D012900:Smallpox Vaccine / Q000276:immunology*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014615:Vaccinia / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000145:classification / Q000276:immunology* / Q000502:physiology; D015047:Zoonoses / Q000821:virology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D012900:Smallpox Vaccine; D007371:Interferon-gamma