Epitopes described in "Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes."

Article Authors:Hema S Bashyam; Sharone Green; Alan L Rothman
Article Title:Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes.
Reference Detail
Reference ID:1001347
Abstract:Reactivation of serotype cross-reactive CD8+ memory T lymphocytes is thought to contribute to the immunopathogenesis of dengue disease during secondary infection by a heterologous serotype. Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination. All four donors had the highest cytokine response to the epitope NS4b 2353. We also studied the effect of sequence differences in heterologous dengue serotypes on dengue-reactive CD8+ memory T cell cytokine and proliferative responses. The D3 variant of a different NS4b epitope 2423 and the D2 variant of the NS4a epitope 2148 induced the largest cytokine response, compared with their respective heterologous sequences in all donors regardless of the primary vaccination serotype. Stimulation with variant peptides also altered the relative frequencies of the various subsets of cells that expressed IFN-gamma, TNF-alpha, MIP-1beta, and combinations of these cytokines. These results indicate that the prior infection history of the individual as well as the serotypes of the primary and heterologous secondary viruses influence the nature of the secondary response. These differences in the effector functions of serotype cross-reactive memory T cells induced by heterologous variant epitopes, which are both quantitative and qualitative, may contribute to the clinical outcome of secondary dengue infection.
Affiliations:Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Reference Type:Literature
PubMed ID:16493038
Journal:J Immunol
Journal Volume:176
Article Pages:2817-24
Journal ISSN:0022-1767
Article Chemical List:Chemokine CCL4;Epitopes, T-Lymphocyte;HLA-A Antigens;HLA-A*02:01 antigen;HLA-A2 Antigen;Macrophage Inflammatory Proteins;Tumor Necrosis Factor-alpha;Interferon-gamma
Article MeSH List:CD8-Positive T-Lymphocytes(immunology; metabolism; virology); Cells, Cultured; Chemokine CCL4; Dengue Virus(classification; immunology); Epitopes, T-Lymphocyte(genetics; immunology); Genetic Variation; HLA-A Antigens(immunology); HLA-A2 Antigen; Humans; Interferon-gamma(biosynthesis; genetics); Macrophage Inflammatory Proteins(biosynthesis; genetics); Serologic Tests; Tumor Necrosis Factor-alpha(biosynthesis; genetics)
Curation Last Updated:2016-03-02 20:01:51