Human CD8+ T-Cell Responses Against the 4 Dengue Virus Serotypes Are Associated With Distinct Patterns of Protein Targets

J Infect Dis. 2015 Dec 1;212(11):1743-51. doi: 10.1093/infdis/jiv289. Epub 2015 May 15.


Background: All 4 dengue virus (DENV) serotypes are now simultaneously circulating worldwide and responsible for up to 400 million human infections each year. Previous studies of CD8(+) T-cell responses in HLA-transgenic mice and human vaccinees demonstrated that the hierarchy of immunodominance among structural versus nonstructural proteins differs as a function of the infecting serotype. This led to the hypothesis that there are intrinsic differences in the serotype-specific reactivity of CD8(+) T-cell responses.

Methods: We tested this hypothesis by analyzing serotype-specific CD8(+) T-cell reactivity in naturally infected human donors from Sri Lanka and Nicaragua, using ex vivo interferon γ-specific enzyme-linked immunosorbent spot assays.

Results: Remarkably similar and clear serotype-specific patterns of immunodominance in both cohorts were identified. Pooling of epitopes that accounted for 90% of the interferon γ response in both cohorts resulted in a global epitope pool. Its reactivity was confirmed in naturally infected donors from Brazil, demonstrating its global applicability.

Conclusions: This study provides new insight into differential serotype-specific immunogenicity of DENV proteins. It further provides a potentially valuable tool for future investigations of CD8(+) T-cell responses in the typically small sample volumes available from patients with acute fever and children without requiring prior knowledge of either infecting DENV serotype or HLA type.

Keywords: Brazil; CD8+ T cells; Nicaragua; Sri Lanka; dengue virus; serotype specific.

Publication types

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

MeSH terms

  • Brazil
  • CD8-Positive T-Lymphocytes / immunology*
  • Dengue / epidemiology*
  • Dengue / immunology*
  • Dengue Virus / classification
  • Dengue Virus / immunology*
  • Humans
  • Serogroup
  • Sri Lanka
  • Viral Proteins / immunology*


  • Viral Proteins