Tumor-associated antigen–HLA class I complex (TAA-HLA-I) (TAA-HLA-I)

The Tumor-associated antigen–HLA class I complex (TAA-HLA-I) is a molecular assembly on the surface of tumor cells consisting of a processed peptide fragment derived from a tumor protein bound to a Human Leukocyte Antigen (HLA) class I molecule (Frontiers in Immunology, 2021). This complex serves as the primary signal for the adaptive immune system, specifically allowing CD8+ cytotoxic T cells to recognize and eliminate malignant cells via their T-cell receptors (TCRs) (Nature Reviews Cancer, 2017). While traditional tumor-associated antigens (TAAs) may be shared across patients, patient-specific versions often refer to neoantigens arising from unique somatic mutations (Nature Reviews Cancer, 2017). Therapeutic strategies targeting these complexes include TCR-engineered T cells (TCR-T), bispecific T-cell engagers such as ImmTACs, and personalized cancer vaccines (FDA, 2022; FDA, 2024). These therapies aim to overcome the limitations of traditional antibodies, which can only target surface proteins, by accessing the intracellular proteome presented via HLA (Frontiers in Immunology, 2021). However, the high specificity required poses challenges, as cross-reactivity with similar peptides in healthy tissues can lead to severe adverse events (Journal of Clinical Oncology, 2013). Additionally, tumors often evade these therapies by downregulating HLA expression or mutating the antigen processing machinery (Nature Reviews Cancer, 2017).

Other names

Neoantigen–HLA class I complexPeptide-MHC class I complexpMHCIpHLA complexTumor-specific antigen–HLA complexAntigen-presenting complex

T-cell receptor (TCR) mediated recognition and activation of cytotoxic T lymphocytes to induce tumor cell lysis.