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J Infect Dis. 2016 Oct 1;214(7):1117-24. doi: 10.1093/infdis/jiw309. Epub 2016 Jul 20.

HLA-DRB1 Alleles Are Associated With Different Magnitudes of Dengue Virus-Specific CD4+ T-Cell Responses.

Author information

1
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, California.
2
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, California Genetech Research Institute.
3
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
4
Department of Zoology and Environmental Science, Science Faculty, University of Colombo.
5
North Colombo Teaching Hospital, Ragama.
6
National Institute of Infectious Diseases, Gothatuwa, Sri Lanka.

Abstract

BACKGROUND:

Each year dengue virus (DENV) infects 400 million human but causes symptomatic disease in only a subset of patients, suggesting that host genetic factors may play a role. HLA molecules that restrict T-cell responses are one of the most polymorphic host factors in humans.

METHODS:

Here we map HLA DRB1-restricted DENV-specific epitopes in individuals previously exposed to DENV, to identify the breadth and specificity of CD4(+) T-cell responses. To investigate whether HLA-specific variations in the magnitude of response might predict associations between dengue outcomes and HLA-DRB1 alleles, we assembled samples from hospitalized patients with known severity of disease.

RESULTS:

The capsid protein followed by nonstructural protein 3 (NS3), NS2A, and NS5 were the most targeted proteins. We further noticed a wide variation in magnitude of T-cell responses as a function of the restricting DRB1 allele and found several HLA alleles that showed trends toward a lower risk of hospitalized disease were associated with a higher magnitude of T-cell responses.

CONCLUSIONS:

Comprehensive identification of unique CD4(+) T-cell epitopes across the 4 DENV serotypes allows the testing of T-cell responses by use of a simple, approachable technique and points to important implications for vaccine design.

KEYWORDS:

CD4+ T cells; Dengue virus; HLA; disease association

PMID:
27443615
PMCID:
PMC5021234
DOI:
10.1093/infdis/jiw309
[Indexed for MEDLINE]
Free PMC Article

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