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Article
Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a
GSBS Student Publications
  • Anuja Mathew, University of Massachusetts Medical School
  • Ichiro Kurane
  • Alan L. Rothman, University of Massachusetts Medical School
  • Lingling Zeng
  • Margo A. Brinton
  • Francis A. Ennis, University of Massachusetts Medical School
UMMS Affiliation
Division of Infectious Diseases and Immunology
Date
10-1-1996
Document Type
Article
Medical Subject Headings
Adult; CD8-Positive T-Lymphocytes; Cells, Cultured; Dengue Virus; Flavivirus; HLA Antigens; Histocompatibility Antigens Class I; Humans; *Immunodominant Epitopes; *Immunologic Memory; Lymphocyte Activation; RNA Helicases; Serine Endopeptidases; Serotyping; T-Lymphocytes, Cytotoxic; Viral Nonstructural Proteins; Viral Vaccines
Abstract

A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the donors had specific T cell proliferation to dengue and to other flaviviruses that we tested. CTLs were generated from the stimulated PBMC of all donors, and in the seven donors tested, dengue virus-specific CD8+CTL activity was demonstrated. The nonstructural (NS3 and NS1.2a) and envelope (E) proteins were recognized by CD8+CTLs from six, five, and three donors, respectively. All donors recognized either NS3 or NS1.2a. In one donor who received a dengue 4 vaccine, CTL killing was seen in bulk culture against the premembrane protein (prM). This is the first demonstration of a CTL response against the prM protein. The CTL responses using the PBMC of two donors were serotype specific, whereas all other donors had serotype-cross-reactive responses. For one donor, CTLs specific for E, NS1.2a, and NS3 proteins were all HLA-B44 restricted. For three other donors tested, the potential restricting alleles for recognition of NS3 were B38, A24, and/or B62 and B35.These results indicate that the CD8+CTL responses of humans after immunization with one serotype of dengue virus are diverse and directed against a variety of proteins. The NS3 and NS1.2a proteins should be considered when designing subunit vaccines for dengue.

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Citation: J Clin Invest. 1996 Oct 1;98(7):1684-91. Link to article on publisher's site
Related Resources
Link to article in PubMed
PubMed ID
8833919
Citation Information
Anuja Mathew, Ichiro Kurane, Alan L. Rothman, Lingling Zeng, et al.. "Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a" Vol. 98 Iss. 7 (1996) ISSN: 0021-9738 (Print)
Available at: http://works.bepress.com/alan_rothman/18/