1. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells.
- Author
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Weiskopf D, Angelo MA, de Azeredo EL, Sidney J, Greenbaum JA, Fernando AN, Broadwater A, Kolla RV, De Silva AD, de Silva AM, Mattia KA, Doranz BJ, Grey HM, Shresta S, Peters B, and Sette A
- Subjects
- Adult, DNA Primers genetics, Dengue Virus genetics, Enzyme-Linked Immunosorbent Assay, Enzyme-Linked Immunospot Assay, Flow Cytometry, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I metabolism, Humans, Monocytes metabolism, Polyproteins immunology, Polyproteins metabolism, Seroepidemiologic Studies, Sri Lanka epidemiology, CD8-Positive T-Lymphocytes immunology, Dengue epidemiology, Dengue immunology, Dengue Virus immunology, Histocompatibility Antigens Class I immunology, Immunologic Memory immunology
- Abstract
The role of CD8(+) T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8(+) responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFNγ responses associated with more than 400 epitopes, challenges the original antigenic sin theory. Although skewing of responses toward primary infecting viruses was detected, this was not associated with impairment of responses either qualitatively or quantitatively. Furthermore, we demonstrate higher magnitude and more polyfunctional responses for HLA alleles associated with decreased susceptibility to severe disease, suggesting that a vigorous response by multifunctional CD8(+) T cells is associated with protection from dengue virus disease.
- Published
- 2013
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