T-cell receptor recognizing FLU-v peptide–MHC complexes (TCR-FLU-v)

The T-cell receptor (TCR) recognizing FLU-v peptide–MHC complexes is the primary molecular target for the FLU-v universal influenza vaccine, which is designed to provide broad protection against multiple influenza strains (Pleguezuelos et al., 2020, The Lancet Infectious Diseases). FLU-v is a synthetic peptide vaccine containing four highly conserved sequences derived from internal influenza virus proteins: Matrix protein 1 (M1), Nucleoprotein (NP), and the Polymerase proteins PA and PB1 (ClinicalTrials.gov, NCT02962934). These peptides are presented by Major Histocompatibility Complex (MHC) Class I and II molecules to T-cells, where the TCR recognizes the specific peptide-MHC complex and initiates an immune signaling cascade. This interaction leads to the activation and expansion of both CD4+ helper and CD8+ cytotoxic T-lymphocytes, resulting in the secretion of effector cytokines such as interferon-gamma (IFN-γ) and granzyme B (Sticchi et al., 2021, Vaccines). Unlike traditional seasonal vaccines that target the rapidly mutating surface protein hemagglutinin, this TCR-mediated approach targets internal proteins that remain stable across different influenza A and B strains, including those with pandemic potential (Pervasive Health, 2024). By activating these specific TCRs, the vaccine induces a cellular memory response that allows the immune system to identify and destroy infected cells regardless of the virus's surface mutations. Clinical trials have demonstrated that the activation of these TCRs correlates with a significant reduction in viral load and the severity of clinical symptoms in subjects challenged with influenza.

Other names

FLU-v specific T-cell receptorInfluenza-specific T-cell receptorTCR recognizing conserved influenza peptides

The FLU-v vaccine provides synthetic peptides that are processed and presented by MHC Class I and II molecules on the surface of antigen-presenting cells; these peptide-MHC complexes then bind to and activate specific T-cell receptors (TCRs) on CD4+ and CD8+ T-lymphocytes, inducing a broad-spectrum cellular immune response against conserved internal influenza antigens.