T-cell receptor recognizing influenza peptide–major histocompatibility complex (TCR-influenza pMHC)

T-cell receptors (TCRs) recognizing influenza peptide–major histocompatibility complex (pMHC) are specialized surface proteins on T lymphocytes that mediate the cellular immune response against influenza viruses. These receptors specifically identify viral protein fragments, most notably the highly conserved matrix protein 1 (M1) peptide, when displayed on the surface of infected cells by MHC Class I molecules such as HLA-A*02:01 (Gras et al., 2009, J. Immunol.). The interaction between the TCR and the pMHC complex initiates intracellular signaling that activates the T cell to perform effector functions, including the release of perforins and granzymes to induce apoptosis in the target cell and the production of cytokines like IFN-gamma (Stewart-Jones et al., 2003, J. Exp. Med.). In therapeutic research, these TCRs are primary targets for the development of TCR-engineered T-cell (TCR-T) therapies and universal vaccines designed to provide long-lasting immunity against diverse influenza strains by targeting conserved epitopes (Koutsakos et al., 2019, Nature Immunology). While promising, the clinical application of these targets faces hurdles such as the requirement for specific HLA matching in patients and the risk of off-target toxicity if the TCR cross-reacts with similar human self-peptides (Nauerth et al., 2013, Science Translational Medicine). Understanding the structural basis of this recognition is essential for designing effective immunotherapies against seasonal and pandemic influenza.

Other names

Influenza-specific T-cell receptorIAV-specific TCRM1-specific T-cell receptorHLA-restricted influenza TCRInfluenza peptide-MHC specific TCR

Recognition of influenza-derived peptides (e.g., M1 58-66) presented by MHC Class I molecules, triggering T-cell receptor signaling, activation of cytotoxic T lymphocytes, and targeted lysis of virus-infected cells.