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

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

Author information

1
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology.
2
Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministerio de Salud.
3
Division of Clinical Immunology and Allergy (LIM-60), School of Medicine, University of São Paulo, Brazil.
4
Sustainable Sciences Institute, Managua, Nicaragua.
5
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology Genetech Research Institute, Colombo, Sri Lanka.
6
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California-Berkeley.

Abstract

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

PMID:
25980035
PMCID:
PMC4633759
DOI:
10.1093/infdis/jiv289
[Indexed for MEDLINE]
Free PMC Article

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