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

Weiskopf D, Angelo MA, Grifoni A, O'Rourke PH, Sidney J, Paul S, De Silva AD, Phillips E, Mallal S, Premawansa S, Premawansa G, Wijewickrama A, Peters B, Sette A
J Infect Dis. 2016 214 (7): 1117-24

PMID: 27443615 · PMCID: PMC5021234 · DOI:10.1093/infdis/jiw309

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.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

MeSH Terms (7)

Adult CD4-Positive T-Lymphocytes Dengue Dengue Virus Epitopes, T-Lymphocyte HLA-DRB1 Chains Humans

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