T-cell receptor recognizing Dengue virus peptide-MHC class I complex (TCR-DENV-pMHC-I)

The T-cell receptor (TCR) recognizing Dengue virus (DENV) peptide-MHC class I complexes is a specialized immune receptor found on the surface of CD8+ cytotoxic T lymphocytes. Its primary biological function is the surveillance and elimination of DENV-infected cells by recognizing viral peptides, predominantly derived from non-structural proteins such as NS3, NS4B, and NS5, which are presented by Human Leukocyte Antigen (HLA) class I molecules on the surface of antigen-presenting cells or infected host cells. Upon binding to its cognate peptide-MHC ligand, the TCR initiates an intracellular signaling cascade that results in the secretion of pro-inflammatory and antiviral cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), and the direct lysis of infected cells via the release of perforin and granzymes. While these responses are generally protective during primary infection, they are heavily implicated in the immunopathology of severe dengue (Dengue Hemorrhagic Fever and Dengue Shock Syndrome) through a phenomenon known as Original Antigenic Sin. In secondary infections with a different DENV serotype, preexisting cross-reactive memory T cells with low affinity for the new serotype may dominate the response, leading to ineffective viral control and a cytokine storm that increases vascular permeability. Therapeutic development focuses on vaccines, such as TAK-003 and Butantan-DV, which aim to elicit robust and high-avidity T-cell responses to conserved epitopes to provide cross-protective immunity across all four DENV serotypes.

Other names

Dengue-specific T-cell receptorDENV-specific CD8+ T-cell receptorCD8+ TCR recognizing DENV pMHC-IDengue virus-specific cytotoxic T-lymphocyte receptor

Activation of CD8+ T cells through the specific recognition of viral peptides presented by MHC class I molecules, leading to the production of antiviral cytokines and the targeted destruction of infected cells.