We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Strong HLA Class I--Restricted T Cell Responses in Dengue Hemorrhagic Fever: A Double-Edged Sword?
- Authors
Loke, Hsin; Bethell, Delia B.; Phuong, C.X.T.; Minh Dung; Schneider, Joerg; White, Nicholas J.; Day, Nicholas P.; Farrar, Jeremy; Hill, Adrian V.S.
- Abstract
Dengue is an increasingly important cause of morbidity and mortality in the tropics, but vac-cine development has been impeded by a poor understanding of disease pathogenesis and, in particular, of immunologic enhancement. In a large case-control study of Vietnamese patients with dengue hemorrhagic fever (DHF), variation at the HLA-A locus was significantly associ-ated with susceptibility to DHF (P 1/4:02), and specific HLA-A susceptibility and resistance alleles were identified. HLA-A--specific epitopes were predicted from binding motifs, and ELI-SPOT analyses of patients with DHF revealed high frequencies of circulating CD8 T lympho-cytes that recognized both serotype-specific and cross-reactive dengue virus epitopes. Thus, strong CD8 T cell responses are induced by natural dengue virus infection, and HLA class I genetic variation is a risk factor for DHF. These genetic and immunologic data support both protective and pathogenic roles for dengue virus--specific CD8 T cell responses in severe dis-ease. The potentially pathogenic role of serotype--cross-reactive CD8 T cells poses yet another obstacle to successful dengue vaccine development.
- Subjects
VIETNAM; DENGUE; HLA histocompatibility antigens
- Publication
Journal of Infectious Diseases, 2001, Vol 184, Issue 11, p1369
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/324320