T-cell receptor on CD8+ cytotoxic T cells recognizing influenza-derived peptides on HLA class I (TCR)

The T-cell receptor (TCR) on CD8+ cytotoxic T cells is a specialized heterodimeric surface protein that mediates the recognition of influenza virus-infected cells (UniProt, 2023). It specifically identifies viral peptides, such as the highly conserved Matrix 1 (M1) 58-66 epitope (GILGFVFTL), when presented by Human Leukocyte Antigen (HLA) class I molecules (PubMed: 28250441). The most common presentation occurs via HLA-A*02:01, a prevalent allele in many human populations. Upon binding to the peptide-MHC complex, the TCR initiates intracellular signaling via the CD3 complex, leading to T-cell activation and the subsequent destruction of the infected cell through the release of perforin and granzymes (NIH, 2022). In therapeutic development, these TCRs are being utilized in TCR-engineered T-cell (TCR-T) therapies to provide robust immunity against severe influenza or as models for understanding cross-reactive T-cell responses (Nature Communications, 2018). The specificity of this interaction is a critical determinant of viral clearance and the prevention of severe respiratory disease (PubMed: 31043487). However, therapeutic application faces challenges such as HLA restriction and the potential for off-target effects if the TCR cross-reacts with similar human peptides (Frontiers in Immunology, 2021). Monitoring TCR repertoire and HLA status is essential for the efficacy and safety of these immunotherapies.

Other names

Influenza-specific T-cell receptorFlu-specific TCRM1-specific TCRHLA-restricted T-cell receptorCD8+ T-cell receptor

The T-cell receptor specifically binds to influenza-derived peptides, such as the M1 58-66 epitope, presented by HLA class I molecules on the surface of infected cells. This binding event triggers a signaling cascade through the associated CD3 complex, leading to the activation of the CD8+ T cell. Once activated, the T cell releases cytotoxic molecules like perforin and granzymes, which induce apoptosis in the virus-infected target cell.