Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein

10Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

Abstract

Immunopathogenesis of dengue virus (DEN) infection remains poorly studied. Identification and characterization of human CD8+ T-cell epitopes on DEN are necessary for a better understanding of the immunopathogenesis of dengue infection and would facilitate the development of immunotherapy and vaccines to protect from dengue infection. Here, we identified two new HLA-A*0201-restricted CD8+ T-cell epitopes, DEN-4 NS1990-998 and DEN-4 NS1997-1005 that are conserved in three or four major DEN serotypes, respectively. Unexpectedly, we found that immunization of HLA-A*0201 transgenic mice with DEN-4 NS1990-998 or DEN-4 NS1997-1005 epitope peptide induced de novo synthesis of tumor necrosis factor (TNF)-α and IFN-γ, two important pro-inflammatory molecules that are hard to be detected directly without in vitro antigenic re-stimulation. Importantly, we demonstrated that CD8+ T cells specifically activated by DEN-4 NS1990-998 or DEN-4 NS1997-1005 epitope peptide induced de novo synthesis of perforin. Furthermore, we observed that DEN-4 NS1990-998 or DEN-4 NS1997-1005-specific CD8+ T cells capable of producing large amounts of perforin, TNF-α and IFN-γ preferentially displayed CD27+CD45RA-, but not CD27-CD45RA+, phenotypes. This study, therefore, suggested the importance of synergistic effects of pro-inflammatory cytokines and cytotoxic molecules which were produced by dengue-specific CD8+ T cells in immunopathogenesis or anti-dengue immunity during dengue infection. © The Japanese Society for Immunology. 2012. All rights reserved.

Cite

CITATION STYLE

APA

Tian, J., Zeng, G., Pang, X., Liang, M., Zhou, J., Fang, D., … Jiang, L. (2012). Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein. International Immunology, 24(4), 207–218. https://doi.org/10.1093/intimm/dxr115

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free