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Conserved epitopes with high HLA-I population coverage are targets of CD8+ T cells associated with high IFN-γ responses against all dengue virus serotypes.
Adikari, Thiruni N; Di Giallonardo, Francesca; Leung, Preston; Grifoni, Alba; Sette, Alex; Weiskopf, Daniela; Bull, Rowena A; Luciani, Fabio.
Afiliación
  • Adikari TN; Immunogenomics Laboratory, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia.
  • Di Giallonardo F; School of Medical Sciences, University of New South Wales, Sydney, Australia.
  • Leung P; Immunogenomics Laboratory, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia.
  • Grifoni A; Immunogenomics Laboratory, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia.
  • Sette A; School of Medical Sciences, University of New South Wales, Sydney, Australia.
  • Weiskopf D; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Bull RA; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Luciani F; Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Sci Rep ; 10(1): 20497, 2020 11 24.
Article en En | MEDLINE | ID: mdl-33235334
Cytotoxic CD8+ T cells are key for immune protection against viral infections. The breadth and cross-reactivity of these responses are important against rapidly mutating RNA viruses, such as dengue (DENV), yet how viral diversity affect T cell responses and their cross-reactivity against multiple variants of the virus remains poorly defined. In this study, an integrated analysis was performed to map experimentally validated CD8+ T cell epitopes onto the distribution of DENV genome sequences across the 4 serotypes worldwide. Despite the higher viral diversity observed within HLA-I restricted epitopes, mapping of 609 experimentally validated epitopes sequences on 3985 full-length viral genomes revealed 19 highly conserved epitopes across the four serotypes within the immunogenic regions of NS3, NS4B and NS5. These conserved epitopes were associated with a higher magnitude of IFN-γ response when compared to non-conserved epitopes and were restricted to 13 HLA class I genotypes, hence providing high coverage among human populations. Phylogeographic analyses showed that these epitopes are largely conserved in most of the endemic regions of the world, and with only some of these epitopes presenting distinct mutated variants circulating in South America and Asia.This study provides evidence for the existence of highly immunogenic and conserved epitopes across serotypes, which may impact design of new universal T-cell-inducing vaccine candidates that minimise detrimental effects of viral diversification and at the same time induce responses to a broad human population.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Interferón gamma / Secuencia Conservada / Linfocitos T CD8-positivos / Virus del Dengue / Serogrupo / Epítopos Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Interferón gamma / Secuencia Conservada / Linfocitos T CD8-positivos / Virus del Dengue / Serogrupo / Epítopos Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido