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    Partial agonist effect influences the CTL response to a heterologous dengue virus serotype

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    Authors
    Zivny, Jaroslav
    DeFronzo, Matthew
    Jarry, William
    Jameson, Julie Marie
    Cruz, John
    Ennis, Francis A.
    Rothman, Alan L.
    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Diseases and Immunology
    Department of Medicine, Division of Gastroenterology
    Center for Infectious Disease and Vaccine Research
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    1999-08-24
    Keywords
    Adult; Clone Cells; Cytotoxicity, Immunologic; Dengue Virus; Epitopes, T-Lymphocyte; Humans; Immunologic Memory; Lymphocyte Activation; Peptide Fragments; RNA Helicases; Serine Endopeptidases; Serotyping; T-Lymphocytes, Cytotoxic; Time Factors; Viral Nonstructural Proteins
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://www.jimmunol.org/content/163/5/2754.long
    Abstract
    Activation of dengue serotype-cross-reactive memory CTL during secondary dengue virus (DV) infection is thought to be important in the pathogenesis of dengue hemorrhagic fever. To model this effect, we studied the CTL responses to DV types 2 (D2V) and 3 (D3V) in PBMC from an individual previously infected with D3V. DV-specific CD8+ CTL from this donor recognized two HLA-B62-restricted epitopes on the NS3 protein, aa 71-79 (SVKKDLISY) and 235-243 (AMKGLPIRY). Both D3V-specific and D2V/D3V-cross-reactive CTL clones were detected for each epitope; all D2V-reactive CTL clones could lyse D2V-infected autologous cells. CTL responses to both epitopes were detected in bulk cultures stimulated with D3V, but PBMC stimulated with D2V recognized only the 235-243 epitope. IFN-gamma enzyme-linked immunospot assay showed that the D2V (71-79) peptide (DVKKDLISY) did not efficiently activate T cells. Analysis of a CTL clone suggests that the D2V (71-79) peptide acts as a partial agonist, able to sensitize target cells for lysis and inducing only minimal proliferation at high concentrations. These results suggest that variant peptide sequences present in the heterologous DV serotype can influence the CTL response in vivo during secondary DV infection.
    Source

    J Immunol. 1999 Sep 1;163(5):2754-60.

    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34014
    PubMed ID
    10453018
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