Tumor-associated antigen–HLA-A2.1 complex (TAA-HLA-A2.1)

Tumor-associated antigen–HLA-A2.1 complexes are specialized molecular structures on the surface of malignant cells that consist of a peptide fragment derived from a tumor-associated antigen (TAA) bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule (Source: National Cancer Institute). These complexes are essential for the adaptive immune system, as they allow CD8+ cytotoxic T cells to recognize and eliminate cells expressing abnormal or overexpressed internal proteins (Source: Abbas et al., Cellular and Molecular Immunology, 2021). HLA-A2.1 is one of the most common MHC Class I alleles in human populations, particularly in Caucasians, making it a primary target for the development of T-cell receptor (TCR)-based therapies (Source: Nature Reviews Drug Discovery, 2022). Therapeutic agents such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers (e.g., ImmTACs) are designed to bind these specific peptide-MHC combinations with high affinity and specificity (Source: Drugs, 2022). The "Other" designation typically refers to a broad range of TAAs—such as NY-ESO-1, MAGE-A4, PRAME, and gp100—that can be presented by HLA-A2.1 to trigger an immune response. While highly promising, targeting these complexes carries risks of off-target toxicity if the targeted peptide is shared with proteins in healthy tissues, as well as the potential for tumor resistance through HLA downregulation (Source: Journal for ImmunoTherapy of Cancer, 2023).

Other names

Other tumor-associated antigen–HLA-A2.1 complexes on tumor cellsPeptide-HLA-A*02:01 complexpMHC complexTumor antigen-MHC class I complexHLA-A2-restricted tumor antigen

Drugs targeting these complexes typically utilize T-cell receptor (TCR) mimicry or engineered TCRs to recognize the specific peptide-MHC combination, leading to T-cell mediated lysis of the tumor cell (Source: Nature Reviews Drug Discovery, 2022).