title: Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection.
abstract: Infection with one of the four dengue virus serotypes (DENV1-4) presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed "original antigenic sin," secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response. The goal of our study was to compare the roles of serotype-specific and cross-reactive T cells in protection vs. pathogenesis during DENV infection in vivo. Specifically, we utilized IFN-α/βR-/-HLA*B0702 transgenic mice in the context of peptide vaccination with relevant human CD8 T cell epitopes. IFN-α/βR-/-HLA*B0702 transgenic mice were immunized with DENV serotype 2 (DENV2)-specific epitopes or variants found in any of the other three serotypes (DENV1, DENV3 or DENV4), followed by challenge with DENV. Although cross-reactive T cell responses were lower than responses elicited by serotype-specific T cells, immunization with either serotype-specific or variant peptide epitopes enhanced viral clearance, demonstrating that both serotype-specific and cross-reactive T cells can contribute to protection in vivo against DENV infection.
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: Annie
authors.initials: A
authors.lastname: Elong Ngono
authors.affiliation: Department of Veterinary Medicine, National Taiwan University, Taiwan.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: William W
authors.initials: WW
authors.lastname: Tang
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: Yunichel
authors.initials: Y
authors.lastname: Joo
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: King
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weiskopf
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States. Electronic address: sujan@lji.org.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003715:Dengue / Q000276:immunology* / Q000378:metabolism*; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015235:HLA-B Antigens / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D065288:Serogroup
chemical_list: D016207:Cytokines; D015235:HLA-B Antigens; D016056:Immunodominant Epitopes
keywords: Cross-reactivity; Dengue; T cells; Vaccination