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Title: | Human CD8(+) T-Cell Responses Against the 4 Dengue Virus Serotypes Are Associated With Distinct Patterns of Protein Targets |
Authors: | WEISKOPF, Daniela; CERPAS, Cristhiam; ANGELO, Michael A.; BANGS, Derek J.; SIDNEY, John; PAUL, Sinu; PETERS, Bjoern; SANCHES, Francoise P.; SILVERA, Cassia G. T.; COSTA, Priscilla R.; KALLAS, Esper G.; GRESH, Lionel; SILVA, Aruna D. de; BALMASEDA, Angel; HARRIS, Eva; SETTE, Alessandro |
Citation: | JOURNAL OF INFECTIOUS DISEASES, v.212, n.11, p.1743-1751, 2015 |
Abstract: | Background. All 4 dengue virus (DENV) serotypes are now simultaneously circulating worldwide and responsible for up to 400 million human infections each year. Previous studies of CD8(+) T-cell responses in HLA-transgenic mice and human vaccinees demonstrated that the hierarchy of immunodominance among structural versus nonstructural proteins differs as a function of the infecting serotype. This led to the hypothesis that there are intrinsic differences in the serotype-specific reactivity of CD8+ T-cell responses. Methods. We tested this hypothesis by analyzing serotype-specific CD8(+) T-cell reactivity in naturally infected human donors from Sri Lanka and Nicaragua, using ex vivo interferon.-specific enzyme-linked immunosorbent spot assays. Results. Remarkably similar and clear serotype-specific patterns of immunodominance in both cohorts were identified. Pooling of epitopes that accounted for 90% of the interferon. response in both cohorts resulted in a global epitope pool. Its reactivity was confirmed in naturally infected donors from Brazil, demonstrating its global applicability. Conclusions. This study provides new insight into differential serotype-specific immunogenicity of DENV proteins. It further provides a potentially valuable tool for future investigations of CD8+ T-cell responses in the typically small sample volumes available from patients with acute fever and children without requiring prior knowledge of either infecting DENV serotype or HLA type. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - LIM/60 Artigos e Materiais de Revistas Científicas - ODS/03 |
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