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

Abstract 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 mu...

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Autores principales:	Thiruni N. Adikari, Francesca Di Giallonardo, Preston Leung, Alba Grifoni, Alex Sette, Daniela Weiskopf, Rowena A. Bull, Fabio Luciani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/51745d141be148b08de2cd69f032174f
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spelling	oai:doaj.org-article:51745d141be148b08de2cd69f032174f2021-12-02T12:33:54ZConserved epitopes with high HLA-I population coverage are targets of CD8+ T cells associated with high IFN-γ responses against all dengue virus serotypes10.1038/s41598-020-77565-22045-2322https://doaj.org/article/51745d141be148b08de2cd69f032174f2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77565-2https://doaj.org/toc/2045-2322Abstract 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.Thiruni N. AdikariFrancesca Di GiallonardoPreston LeungAlba GrifoniAlex SetteDaniela WeiskopfRowena A. BullFabio LucianiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thiruni N. Adikari Francesca Di Giallonardo Preston Leung Alba Grifoni Alex Sette Daniela Weiskopf Rowena A. Bull Fabio Luciani 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
description	Abstract 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.
format	article
author	Thiruni N. Adikari Francesca Di Giallonardo Preston Leung Alba Grifoni Alex Sette Daniela Weiskopf Rowena A. Bull Fabio Luciani
author_facet	Thiruni N. Adikari Francesca Di Giallonardo Preston Leung Alba Grifoni Alex Sette Daniela Weiskopf Rowena A. Bull Fabio Luciani
author_sort	Thiruni N. Adikari
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/51745d141be148b08de2cd69f032174f
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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

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