HLA-A*02:01-melanoma-associated antigen peptide complex (HLA-A*02:01-MAA complex)

The HLA-A*02:01-melanoma-associated antigen peptide complex is a specific molecular target formed by the presentation of intracellular melanoma-derived peptides within the binding groove of the Human Leukocyte Antigen (HLA) A*02:01 allele (IMGT/HLA Database, 2024). This complex is expressed on the surface of melanoma cells and serves as a critical recognition signal for the immune system, specifically for CD8+ cytotoxic T cells (PubMed, PMID: 34551229). Common antigens presented include MART-1, gp100, and MAGE-A4, which are often overexpressed in melanoma but have limited expression in normal tissues (Journal of Immunotherapy of Cancer, 2021). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies and bispecific T-cell engagers, such as Tebentafusp, which are designed to bind the pMHC complex with high affinity and specificity (New England Journal of Medicine, 2021). By bypassing the need for natural T-cell recognition, these drugs redirect the immune system to selectively eliminate tumor cells. However, the high degree of similarity between certain tumor-associated peptides and self-peptides in healthy tissues poses a risk of off-target toxicity (Nature Medicine, 2022). Clinical success has validated this complex as a viable target for immunotherapy in HLA-A*02:01 positive patients (FDA, 2022).

Other names

HLA-A2-melanoma peptide complexpMHC complexHLA-A*02:01/gp100HLA-A*02:01/MAGE-A4HLA-A*02:01/MART-1HLA-A*02:01/NY-ESO-1MHC-peptide complex

T-cell receptor (TCR) mediated recognition and redirection of T-cell cytotoxicity toward peptide-MHC expressing cells (Nature Reviews Drug Discovery, 2023).