CD8+ T-cell receptor specific for HLA-A*0201–Melan-A complex (MART-1 TCR) (Melan-A/HLA-A2 TCR)

The CD8+ T-cell receptor specific for the HLA-A*0201–Melan-A complex is a specialized immune receptor that recognizes a specific peptide fragment of the Melan-A (also known as MART-1) protein presented by the Human Leukocyte Antigen (HLA) allele A*0201 (UniProt Q16655). Melan-A is a differentiation antigen highly expressed in most malignant melanomas, making this TCR-pMHC complex a primary target for adoptive T-cell therapies (Morgan et al., 2006). In a therapeutic context, patients' T cells are genetically engineered to express high-affinity versions of this TCR, such as the DMF5 or F4 clones, to redirect the immune system to identify and destroy melanoma cells (Johnson et al., 2009). While these therapies have demonstrated significant clinical regression in some patients, they are frequently associated with on-target, off-tumor toxicities because Melan-A is also expressed in healthy melanocytes located in the skin, eye, and inner ear (Chodon et al., 2014). Consequently, clinical management often involves monitoring for autoimmune-like side effects such as vitiligo, uveitis, and hearing loss. This target remains a cornerstone of TCR-T cell research, serving as a model for optimizing receptor affinity and managing the safety profiles of antigen-specific immunotherapy.

Other names

MART-1 specific T-cell receptorMelan-A specific TCRHLA-A*02:01/MART-1(26-35) TCRMelanoma antigen recognized by T cells 1 specific TCRDMF5 TCRF4 TCR

Engineered T-cell receptors bind specifically to the Melan-A (MART-1) peptide presented by the HLA-A*0201 molecule on tumor cells, initiating T-cell activation, cytokine secretion, and granzyme-mediated lysis of the target cell (Morgan et al., 2006; Johnson et al., 2009).