Journal article
HLA-DRB1 alleles are associated with different magnitudes of dengue Virus–Specific CD4+T-Cell responses
Journal of Infectious Diseases, Vol.214(7), pp.1117-1124
2016
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.
Details
- Title
- HLA-DRB1 alleles are associated with different magnitudes of dengue Virus–Specific CD4+T-Cell responses
- Authors/Creators
- D. Weiskopf (Author/Creator) - La Jolla Institute for ImmunologyM.A. Angelo (Author/Creator) - La Jolla Institute for ImmunologyA. Grifoni (Author/Creator) - La Jolla Institute for ImmunologyP.H. O'Rourke (Author/Creator) - La Jolla Institute for ImmunologyJ. Sidney (Author/Creator) - La Jolla Institute for ImmunologyS. Paul (Author/Creator) - La Jolla Institute for ImmunologyA.D. De Silva (Author/Creator)E. Phillips (Author/Creator) - Murdoch UniversityS. Mallal (Author/Creator) - Vanderbilt UniversityS. Premawansa (Author/Creator) - University of ColomboG. Premawansa (Author/Creator) - Colombo North Teaching HospitalA. Wijewickrama (Author/Creator) - National Institute of Infectious DiseasesB. Peters (Author/Creator) - La Jolla Institute for ImmunologyA. Sette (Author/Creator) - La Jolla Institute for Immunology
- Publication Details
- Journal of Infectious Diseases, Vol.214(7), pp.1117-1124
- Publisher
- Oxford University Press
- Identifiers
- 991005545555007891
- Copyright
- © 2016 The Author
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
- Additional Information
- Presented in part: 5th Pan American Dengue Research Network Meeting, Panama City, Panama, 20–23 April 2016; Annual Meeting of the American Association of Immunologists, 13–17 May 2016, Seattle, Washington.
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- Citation topics
- 1 Clinical & Life Sciences
- 1.228 Virology - Tropical Diseases
- 1.228.200 Mosquito-borne Viruses
- Web Of Science research areas
- Immunology
- Infectious Diseases
- Microbiology
- ESI research areas
- Immunology