Epitopes described in "Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive."

Article Authors:Heather Friberg; Lynne Burns; Marcia Woda; Siripen Kalayanarooj; Timothy P Endy; Henry A F Stephens; Sharone Green; Alan L Rothman; Anuja Mathew
Article Title:Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive.
Reference Detail
Reference ID:1021171
Abstract:Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to have an immunopathological function in secondary heterologous DENV infection. To define the T-cell response to heterologous serotypes, we isolated HLA-A(*)1101-restricted epitope-specific CD8(+) T-cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity toward peptide variants representing the four DENV serotypes in tetramer binding and functional assays. Many clones responded similarly to homologous and heterologous serotypes with striking cross-reactivity between the DENV-1 and DENV-3 epitope variants. In vitro-stimulated T-cell lines consistently revealed a hierarchical induction of MIP-1>degranulation>tumor necrosis factor (TNF)>interferon- (IFN), which depended on the concentration of agonistic peptide. Phosphoflow assays showed peptide dose-dependent phosphorylation of ERK1/2, which correlated with cytolysis, degranulation, and induction of TNF and IFN, but not MIP-1 production. This is the first study to show significant DENV serotype-cross-reactivity of CD8(+) T cells after naturally acquired primary infection. We also show qualitatively different T-cell receptor signaling after stimulation with homologous and heterologous peptides. Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes.
Reference Type:Literature
PubMed ID:20421879
Journal:Immunol Cell Biol
Journal Volume:89
Article Pages:122-9
Journal ISSN:0818-9641
Article Chemical List:Cytokines;Epitopes;HLA-A Antigens;Receptors, Antigen, T-Cell;Extracellular Signal-Regulated MAP Kinases
Article MeSH List:Adolescent; Amino Acid Sequence; Animals; CD8-Positive T-Lymphocytes(immunology; metabolism); Cell Line; Cross Reactions(immunology); Cytokines(biosynthesis); Dengue(immunology); Epitopes(chemistry; immunology); Extracellular Signal-Regulated MAP Kinases(metabolism); HLA-A Antigens(immunology); Humans; Mice; Mice, Inbred BALB C; Receptors, Antigen, T-Cell(metabolism); Signal Transduction(immunology); Young Adult
Curation Last Updated:2016-03-02 20:20:57