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Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein.
Int Immunol. 2012 Apr; 24(4):207-18.II

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 NS1(990)(-998) and DEN-4 NS1(997)(-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 NS1(990)(-998) or DEN-4 NS1(997)(-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 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of perforin. Furthermore, we observed that DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-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.

Authors+Show Affiliations

Key Laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22298881

Citation

Tian, Jiang, et al. "Identification and Immunogenicity of Two New HLA-A*0201-restricted CD8+ T-cell Epitopes On Dengue NS1 Protein." International Immunology, vol. 24, no. 4, 2012, pp. 207-18.
Tian J, Zeng G, Pang X, et al. Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein. Int Immunol. 2012;24(4):207-18.
Tian, J., Zeng, G., Pang, X., Liang, M., Zhou, J., Fang, D., Liu, Y., Li, 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), 207-18. https://doi.org/10.1093/intimm/dxr115
Tian J, et al. Identification and Immunogenicity of Two New HLA-A*0201-restricted CD8+ T-cell Epitopes On Dengue NS1 Protein. Int Immunol. 2012;24(4):207-18. PubMed PMID: 22298881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein. AU - Tian,Jiang, AU - Zeng,Gucheng, AU - Pang,Xianwu, AU - Liang,Mifang, AU - Zhou,Junmei, AU - Fang,Danyun, AU - Liu,Yan, AU - Li,Dexin, AU - Jiang,Lifang, Y1 - 2012/01/31/ PY - 2012/2/3/entrez PY - 2012/2/3/pubmed PY - 2012/8/4/medline SP - 207 EP - 18 JF - International immunology JO - Int Immunol VL - 24 IS - 4 N2 - 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 NS1(990)(-998) and DEN-4 NS1(997)(-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 NS1(990)(-998) or DEN-4 NS1(997)(-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 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of perforin. Furthermore, we observed that DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-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. SN - 1460-2377 UR - https://www.unboundmedicine.com/medline/citation/22298881/Identification_and_immunogenicity_of_two_new_HLA_A_0201_restricted_CD8+_T_cell_epitopes_on_dengue_NS1_protein_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxr115 DB - PRIME DP - Unbound Medicine ER -