| Reference | ||
|---|---|---|
| Reference Type | Dual | IEDB_Reference:1030032 |
| Title | Identification of MHC class II T Cell Epitopes derived from Dengue Virus | |
| Submission Title | Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity. | |
| Authors | Daniela Weiskopf (1); Michael Angelo (1); Alba Grifoni (1); Patrick O'Rourke (1); John Sidney (1); Sinu Paul (1); Aruna D. De Silva (1,2); Elizabeth Phillips (3); Simon Mallal (3); Sunil Premawansa (4); Gayani Premawansa (5); Ananda Wijewickrama (6); Bjoern Peters (1); Alessandro Sette (1) | |
| Submission Authors | Daniela Weiskopf; Derek J Bangs; John Sidney; Ravi V Kolla; Aruna D De Silva; Aravinda M de Silva; Shane Crotty; Bjoern Peters; Alessandro Sette | |
| Affiliations | (1) Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, United States; (2) Genetech Research Institute, Colombo, 00800, Sri Lanka; (3) Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia 6150, Australia and Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37235, USA; (4) Department of Zoology and Environmental Science, Science Faculty, University of Colombo, Sri Lanka; (5) North Colombo Teaching Hospital, Ragama, Colombo, Sri Lanka; (6) National Institute of Infectious Diseases, Gothatuwa, Angoda, Sri Lanka | |
| Submission Affiliations | Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; daniela@liai.org; Genetech Research Institute, Colombo, 00800, Sri Lanka; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599. | |
| Journal | Proc Natl Acad Sci U S A | |
| Submitter | Kerrie Vaughan | IEDB_Submission:1000699 |
| Year | 2016 | |
| Submission Date | 2015 | |
| Abstract | Background: Each year dengue virus 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 dengue virus to identify the breadth and specificity of CD4+ T cell responses. To investigate if HLA specific variations in magnitude of response might predict associations between DENV disease outcomes and HLA DRB1 alleles, we assembled samples from hospitalized patients known severity of disease. Results: The capsid protein followed by nonstructural NS3, NS2A, and NS5 proteins 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 significantly lower risk of hospitalized disease were associated with a higher magnitude of T cell responses. Conclusions:Results confirmed the association of magnitude of HLA restricted T cell response with protection from disease and knowledge of DENV-specific CD4+ T cells will aid in the establishment of correlates of protection against severe disease. | |
| Submission Abstract | Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8(+) T-cell responses have been extensively studied, the breadth and specificity of CD4(+) T-cell responses remains to be defined. Here we define HLA-restricted CD4(+) T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+) Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4(+) T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development. | |
| Curation Last Updated | 2024-11-04 20:03:31 | |
| Related Information | |
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| Epitopes | |
| Bcell Assays | 0 |
| Tcell Assays | |
| MHC Ligand Assays | |