HLA-A*02:01-Melan-A peptide complex (HLA-A*02:01/Melan-A)

The HLA-A*02:01-Melan-A peptide complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of cells, particularly melanoma cells (UniProt: Q16655). It consists of the HLA-A*02:01 MHC class I molecule and a processed peptide fragment from the Melan-A (also known as MART-1) protein, typically the immunodominant decamer ELAGIGILTV or nonamer AAGIGILTV (PMID: 8134371). This complex serves as a primary target for T-cell based immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific TCR molecules, because Melan-A is highly expressed in most melanomas (PMID: 19171880). The complex is recognized by the TCRs of CD8+ cytotoxic T lymphocytes, which triggers T-cell activation and the subsequent lysis of the presenting tumor cell. While it is a potent target for inducing anti-tumor immune responses, its presence on normal melanocytes in the skin, eye, and inner ear can lead to on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss (PMID: 16946032). Therapeutic strategies aim to exploit the high density of this complex on malignant cells to achieve selective tumor destruction while managing these predictable autoimmune-like side effects. The HLA-A*02:01-Melan-A complex remains one of the most well-characterized pMHC targets in the field of cancer immunotherapy due to the high prevalence of the HLA-A*02:01 allele in Caucasian populations.

Other names

MART-1/HLA-A*02:01 complexMelan-A/HLA-A2 complexHLA-A*02:01-MART-1 peptide complexpMHC HLA-A*02:01/Melan-A26-35

TCR-mediated recognition of the peptide-MHC complex leading to T-cell activation and lysis of the target cell.