Tumor-associated antigen peptide–Human leukocyte antigen-A*02 (TAA-HLA-A*02) complex (TAA-HLA-A*02)

The tumor-associated antigen peptide–Human leukocyte antigen-A*02 (TAA-HLA-A*02) complex is a molecular assembly consisting of a short peptide fragment derived from a tumor-specific or tumor-associated protein bound within the groove of the Human Leukocyte Antigen-A*02 (HLA-A*02) molecule (Janeway et al., 2001). HLA-A*02 is a common Class I Major Histocompatibility Complex (MHC) allele that presents intracellularly processed antigens to CD8+ cytotoxic T lymphocytes, playing a pivotal role in the adaptive immune response (Gonzalez-Galarza et al., 2020). In oncology, these complexes serve as critical flags that allow the immune system to distinguish malignant cells from healthy ones by displaying mutated or overexpressed proteins on the cell surface. Therapeutic strategies targeting these complexes include T-cell receptor (TCR) engineered T-cells, bispecific T-cell engagers (ImmTACs), and TCR-like antibodies, which are designed to recognize the specific peptide-HLA configuration (Nathan et al., 2021). Because HLA-A*02 is highly prevalent in Caucasian populations, it is a primary focus for the development of immunotherapies targeting antigens like gp100, MAGE-A4, and NY-ESO-1 (Merchant et al., 2024). Successful clinical application requires patient screening for the HLA-A*02 genotype and confirmed expression of the target antigen within the tumor.

Other names

pMHC complexPeptide-HLA-A*02 complexAntigen-MHC class I complexHLA-A*02:01-peptide complexTumor antigen-HLA complex

Targeting agents bind the specific peptide-HLA-A*02 complex on the tumor cell surface and simultaneously engage T-cells via the T-cell receptor or CD3, leading to the formation of an immunological synapse and subsequent perforin/granzyme-mediated lysis of the cancer cell (Nathan et al., 2021).