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Dengue virus-specific CD8+ T cells are a critical component of the adaptive immune system responsible for identifying and eliminating cells infected with the Dengue virus (DENV). These cytotoxic T lymphocytes (CTLs) recognize specific viral peptides, primarily derived from non-structural proteins like NS3, which are presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of infected cells (Weiskopf et al., 2013, PNAS). Upon recognition via their T-cell receptors (TCRs), these cells proliferate and deploy effector mechanisms, including the secretion of antiviral cytokines such as interferon-gamma (IFN-γ) and the direct lysis of target cells through perforin and granzymes (Grifoni et al., 2017, Frontiers in Immunology). While essential for viral clearance, these cells are also implicated in the immunopathology of severe Dengue, such as Dengue Hemorrhagic Fever (DHF), through a process known as "original antigenic sin" (Mongkolsapaya et al., 2003, Nature Medicine). In this scenario, memory T cells from a prior infection with one DENV serotype may react poorly to a different serotype during a secondary infection, leading to a massive, ineffective inflammatory response or "cytokine storm" (Rothman, 2011, Nature Reviews Immunology). Consequently, eliciting a balanced and protective CD8+ T-cell response is a primary goal in the development of tetravalent Dengue vaccines like Qdenga and Dengvaxia (Screaton et al., 2015, Nature Reviews Immunology).
Vaccine-mediated priming and activation of CD8+ T cells to recognize and eliminate DENV-infected cells via T-cell receptor (TCR) interaction with viral peptide-MHC class I complexes.
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