title: T cell responses to an HLA-B*07-restricted epitope on the dengue NS3 protein correlate with disease severity.
abstract: Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF than in those who had experienced DF. We also detected peptide-specific T cells in PBMC obtained at the time of the acute DV infection in 2 of 5 subjects. These data suggest that the NS3 (221-232) epitope is an important target of CD8(+) T cells in secondary DV infection and that the activation and expansion of DV-specific T cells is greater in subjects with DHF than in those with dengue fever. These findings support the hypothesis that activation of DV-specific CD8(+) T cells plays an important role in the pathogenesis of DHF.
authors.affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Iva
authors.initials: I
authors.lastname: Zivna
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: Henry A F
authors.initials: HA
authors.lastname: Stephens
authors.forename: Dasnayanee
authors.initials: D
authors.lastname: Chandanayingyong
authors.forename: Ananda
authors.initials: A
authors.lastname: Nisalak
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens / Q000276:immunology*; D015793:HLA-B7 Antigen; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology; D011446:Prospective Studies; D020365:RNA Helicases; D012367:RNA, Viral / Q000097:blood; D012697:Serine Endopeptidases; D013601:T-Lymphocytes / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D015793:HLA-B7 Antigen; D007376:Interleukin-2; D010446:Peptide Fragments; D020365:RNA Helicases; D012367:RNA, Viral; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C425023:HLA-B*07 antigen; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases