Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting melanoma-associated peptides (HLA-A*02:01/Melanoma Peptide Complex)

Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting melanoma-associated peptides is a critical molecular complex involved in the cellular immune recognition of malignant melanoma cells (Nathan et al., 2021, NEJM). HLA-A*02:01 is a specific allele of the Major Histocompatibility Complex (MHC) Class I that binds and displays intracellularly derived peptide fragments, such as those from gp100, MART-1, or MAGE-A4, on the cell surface (PubMed, PMID: 34554640). These peptide-MHC (pMHC) complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T-lymphocytes, triggering an immune response against the tumor (NIH, National Cancer Institute). In therapeutic contexts, this complex serves as a highly specific target for advanced immunotherapies, including bispecific T-cell engagers and TCR-engineered T-cell (TCR-T) therapies (Adaptimmune, 2024). For instance, Tebentafusp is a bispecific protein that redirects T-cells to kill melanoma cells by binding to the gp100 peptide presented by HLA-A*02:01 (FDA, 2022). Targeting these complexes allows for the precision destruction of cancer cells while minimizing damage to healthy tissues that do not express the specific tumor-associated antigens. However, therapeutic efficacy can be challenged by HLA downregulation or loss of antigen expression, which are common mechanisms of tumor immune evasion (Nature Communications, 2020). Patient selection for these therapies requires screening for both the HLA-A*02:01 genotype and the presence of the specific melanoma-associated antigen (StatPearls, 2023).

Other names

HLA-A*02:01-peptide complexMHC Class I HLA-A*02:01pMHC complexMelanoma-associated antigen/HLA-A*02:01 complex

T-cell redirection and activation through high-affinity binding of therapeutic TCR domains to the specific peptide-HLA complex on the tumor cell surface (FDA, 2022).