| Reference | ||
|---|---|---|
| Reference Type | Submission | IEDB_Reference:1024519 |
| Title | Identification of T Cell Epitopes derived from Dengue Virus | |
| Authors | Daniela Weiskopf Ph.D.; Michael A Angelo; Elzinandes L de Azeredo Ph.D.; John Sidney; Jason A Greenbaum Ph.D; Bjoern Peters Ph.D; Alessandro Sette Ph.D | |
| Affiliations | Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA | |
| Submitter | Daniela Weiskopf | IEDB_Submission:1000504 |
| Year | 2012 | |
| Abstract | The frequency of dengue virus (DENV) infection has increased dramatically in the recent decades and the lack of a vaccine has led to significant worldwide morbidity and mortality. The role of T cells in dengue infection is not yet fully understood. One major obstacle to fully elucidate their function is the lack of knowledge of T cell epitopes presented by common MHC alleles expressed by populations in endemic areas. To improve on the minimal information available regarding HLA-restricted T cell responses resulting from natural infection with DENV, we endeavored to map T cell responses in individuals from Sri Lanka where DENV is hyper-epidemic. To cover a wide range of HLA phenotypes we first performed bioinformatics predictions for 16 HLA A and 11 HLA B alleles to identify MHC binding peptides derived from all four serotypes. To validate this approach, we have tested the predicted peptides in an ex vivo ELISPOT assay for their ability to induce an IFN-g response in HLA-matched PBMC of 250 blood donors. This proteome-wide screen has identified a total of 408 epitopes across all 10 DENV proteins (C, M, E, NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). Interestingly, the epitopes are not evenly distributed across the dengue proteome but appear to cluster in discrete regions. Clustering epitopes that share more than 80% sequence homology resulted in the definition of 267 antigenic regions, with the 25 most immunodominant regions already accounting for 50% of the total response observed. Interestingly many of these most immunodominant antigenic regions are not only derived from multiple serotypes but are also restricted by a variety of different alleles. Additionally, we see a wide variation in terms of frequency as well as magnitude between the different HLA alleles. HLA B restricted responses were of significantly higher magnitude and breadth compared to HLA A restricted responses although they were similar in terms of frequency. Our data here provide specific insights and understanding into the nature of HLA-restricted T cell responses and the role of T cells in DENV infection, and suggest future strategies in vaccine design against this globally intensifying viral threat. This work was supported by National Institutes of Health contract Nr. HHSN272200900042C (to A.S.) | |
| Curation Last Updated | 2023-08-18 21:06:31 | |
| Related Information | |
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| Epitopes | |
| Bcell Assays | 0 |
| Tcell Assays | |
| MHC Ligand Assays | 0 |