Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection.
Journal
EBioMedicine
Date Issued
2016
Author(s)
Elong Ngono, Annie
Tang, William W
Joo, Yunichel
King, Kevin
Weiskopf, Daniela
Sidney, John
Sette, Alessandro
Shresta, Sujan
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. ? 2016 The Authors
Subjects
Cross-reactivity; Dengue; T cells; Vaccination
SDGs
Other Subjects
cross reacting antibody; gamma interferon; cytokine; epitope; HLA B antigen; amino acid sequence; animal tissue; antibody response; Article; binding affinity; CD8+ T lymphocyte; controlled study; cytokine production; dengue; Dengue virus; enzyme linked immunospot assay; female; flow cytometry; immune response; immunization; immunogenicity; male; mouse; nonhuman; priority journal; protein binding; reverse transcription polymerase chain reaction; secondary infection; serotype; viral clearance; animal; biosynthesis; CD8+ T lymphocyte; classification; cross reaction; dengue; disease model; immunology; metabolism; phenotype; transgenic mouse; Animals; CD8-Positive T-Lymphocytes; Cross Reactions; Cytokines; Dengue; Dengue Virus; Disease Models, Animal; Female; HLA-B Antigens; Immunodominant Epitopes; Male; Mice; Mice, Transgenic; Phenotype; Serogroup