Tumor-associated antigen peptide–HLA complex and T-cell receptor

The tumor-associated antigen peptide–HLA complex and T-cell receptor is a supramolecular immune recognition system central to adaptive immunity and tumor immunosurveillance. In this complex, a tumor-specific peptide (antigen) is bound within the groove of a human leukocyte antigen (HLA, also known as MHC) molecule on the surface of an antigen-presenting cell or tumor cell. Recognition occurs when the T-cell receptor (TCR), located on the surface of T lymphocytes, specifically binds the peptide–HLA complex with high sensitivity and discriminates between healthy and transformed (tumor) cells[1][2][5]. This binding event triggers T-cell activation, leading to cytotoxic responses and elimination of target cells[1][3][5]. Structural and functional diversity arises from the enormous polymorphism of HLA molecules, peptide variability, and somatic diversification of TCRs, making this interaction both a critical axis for immune tumor control and a challenging therapeutic target. Therapeutic strategies include engineering or redirecting TCRs or TCR-mimic molecules to target specific tumor peptide–HLA complexes, as well as developing peptide-based cancer vaccines to enhance tumor visibility to the T-cell compartment[2][5][6]. Notable therapeutic challenges include the risk of off-target toxicity, immune escape mechanisms, and the need for precise biomarker-driven patient selection.

Other names

Peptide–HLA complex and TCRPeptide–MHC–TCR trimolecular complexTumor antigen–HLA–TCR complexpMHC–TCR complex

Recognition and targeting of tumor-associated peptide–HLA complexes by TCRs on cytotoxic T cells, leading to tumor cell destruction[1][5]. Engineering or redirecting TCRs or antibodies to bind specific tumor peptide–HLA complexes, triggering T-cell mediated killing[6]. Enhancement of antigen presentation to increase visibility to TCRs[3].