Dengue virus-specific CD8 T cell subsets are associated with specialized gene expression profiles and TCR repertoires

Accumulating evidence demonstrates that CD8 T cells contribute to protection from severe DENV disease and vaccine efficacy. Nevertheless, the molecular programs associated with DENV-specific CD8 T cell subsets have not been defined. Here, we studied the transcriptomic profiles of human DENV-specific CD8 T cells isolated after stimulation with DENV epitopes from donors that have been infected with DENV multiple times and should therefore associated with significant levels of adaptive immunity. DENV-specific CD8 T cells mainly consist of effector memory subsets, namely Tem and Temra which enact specific gene expression profiles upon stimulation with cognate antigens. DENV-specific CD8 T cell subsets in general, and Temra cells in particular, are fully activated and polyfunctional, yet associated with relatively narrow transcriptional responses and TCR repertoires. This study provides the first transcriptomic definition of DENV-specific activated human CD8 T cell subsets and defines a bench mark profile that vaccine-specific response could aim to reproduce. RNA-sequencing of sorted unstimulated and dengue virus epitopes-stimulated IFN-gamma+ CD8 Tem and Temra cells from cryopreserved PBMC of 6 subjects with secondary dengue infection.