Human leukocyte antigen A2-Melanoma antigen recognized by T cells 1 peptide complex (HLA-A2-Melan-A)

The HLA-A2–Melan-A peptide complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanoma cells (UniProt: Q16655). It consists of the HLA-A*02:01 molecule presenting a short peptide derived from the Melan-A (also known as MART-1) protein, which is a lineage-specific differentiation antigen (PubMed: 16946036). This complex serves as a critical recognition element for the immune system, specifically for CD8+ T cells expressing T-cell receptors (TCRs) specific to this epitope. In the context of cancer immunotherapy, this complex is a prominent target for TCR-engineered T-cell therapies and bispecific T-cell engagers (Science: 314(5796)). Because Melan-A is highly expressed in most melanomas but has limited expression in normal tissues, it provides a window for therapeutic targeting. However, targeting this complex can lead to autoimmune-like side effects in the skin, eyes, and ears where normal melanocytes reside (Blood: 114(3)). Successful engagement of this target triggers T-cell mediated cytotoxicity, leading to the destruction of the presenting tumor cells. This target is restricted to patients who are HLA-A*02:01 positive, a common haplotype in Caucasian populations.

Other names

HLA-A2-MART-1 complexHLA-A*02:01-MART-1 complexMART-1/HLA-A2 complexMelan-A/HLA-A2 complexHLA-A2-Melan-A peptide complex on melanoma cells

Specific recognition by engineered T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte activation and granzyme/perforin-mediated apoptosis of the target cell (Morgan et al., Science, 2006).