T cell receptor recognizing Influenza A virus Matrix protein 1 (58-66) peptide-HLA-A*02:01 complex (Flu M1-specific TCR)

The T cell receptor (TCR) recognizing the GILGFVFTL peptide is a pivotal component of the human immune response against Influenza A virus. This peptide, spanning residues 58-66 of the viral Matrix protein 1 (M1), is presented by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (Stewart-Jones et al., 2003, Journal of Immunology). The receptor is predominantly found on CD8+ cytotoxic T lymphocytes, where it mediates the recognition and elimination of infected cells. A hallmark of this TCR is its public nature, frequently utilizing the TRBV19 gene segment across different individuals, which makes it a gold-standard model in molecular immunology (Miles et al., 2011, Nature Communications). Upon binding the peptide-MHC complex, the TCR triggers intracellular signaling that leads to T cell proliferation and the release of cytotoxic molecules. In clinical research, this TCR system serves as a template for developing TCR-engineered T cell (TCR-T) therapies and soluble TCR-based drugs. These therapeutic approaches leverage the high specificity of the TCR to redirect the immune system toward specific viral or malignant targets. Understanding the structural basis of this interaction has been crucial for engineering higher-affinity receptors for precision immunotherapy. Safety considerations for such therapies include potential cross-reactivity with similar self-peptides, which could lead to autoimmune-like damage. Overall, this TCR-pMHC system is a cornerstone of adaptive immunity and a primary tool for advancing TCR-based medicine.

Other names

GILGFVFTL-specific TCRM1(58-66)-specific TCRHLA-A*02:01/GILGFVFTL-restricted T cell receptorInfluenza A M1-specific TCRJM22 TCR

The TCR specifically binds to the GILGFVFTL peptide presented by the HLA-A*02:01 molecule on the surface of infected cells. This binding event triggers a signaling cascade through the CD3 complex, leading to the activation of the CD8+ T cell, secretion of cytotoxic granules such as perforin and granzyme, and subsequent apoptosis of the target cell (Gras et al., 2009, Immunity).