HLA-A*02:01-presented Melanoma Antigen Recognized by T cells 1 (MART-1) peptide complex (HLA-A2/MART-1)

The HLA-A*02:01-presented MART-1 (Melanoma Antigen Recognized by T cells 1) peptide complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanoma cells and normal melanocytes (Kawakami et al., 1994, PNAS). It consists of the HLA-A*02:01 molecule, a common Class I MHC allele, bound to an immunodominant peptide derived from the MART-1 protein, also known as Melan-A. This complex serves as a critical target for T-cell receptor (TCR)-based immunotherapies, as it allows the immune system to distinguish melanoma cells from most other healthy tissues. However, because MART-1 is also expressed in healthy melanocytes, therapies targeting this complex can lead to on-target, off-tumor toxicities affecting the skin, eyes, and ears (Johnson et al., 2009, Blood). Clinical development has focused on engineered TCR-T cells designed to recognize this specific pMHC with high affinity and specificity (Morgan et al., 2006, Science). The recognition of this complex by T cells triggers a cascade of immune responses, including the release of perforins and granzymes, leading to the apoptosis of the target cell. This target is particularly significant in the field of adoptive cell transfer and has been a foundational model for developing TCR-engineered therapies. Patient selection for these therapies requires screening for both the HLA-A*02:01 allele and the expression of the MART-1 protein within the tumor.

Other names

HLA-A*02:01/Melan-A complexHLA-A2/MART-1(26-35) complexHLA-A2/MART-1(27-35) complexpMHC complex (HLA-A*02:01/MART-1)

T-cell receptor (TCR) mediated recognition of the pMHC complex, leading to T-cell activation, cytokine release, and cytotoxic lysis of the target cell (Morgan et al., 2006).