Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus

J Immunol. 2015 Sep 1;195(5):2263-72. doi: 10.4049/jimmunol.1402508. Epub 2015 Jul 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Line
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Host-Pathogen Interactions / immunology
  • Immunodominant Epitopes / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice, Inbred C57BL
  • Smallpox Vaccine / immunology*
  • Species Specificity
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / virology
  • Vaccinia / immunology*
  • Vaccinia / virology
  • Vaccinia virus / classification
  • Vaccinia virus / immunology*
  • Vaccinia virus / physiology
  • Zoonoses / virology


  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Smallpox Vaccine
  • Interferon-gamma