Melanoma antigen recognized by T cells 1 peptide-HLA-A*02:01 complex (MART-1/HLA-A2 complex)

The Melanoma antigen recognized by T cells 1 (MART-1) peptide-HLA-A*02:01 complex is a major target for cancer immunotherapy, particularly in malignant melanoma. This complex consists of a specific peptide fragment derived from the MART-1 protein (also known as Melan-A) presented on the cell surface by the Class I Human Leukocyte Antigen (HLA)-A*02:01 molecule (Kawakami et al., 1994, PMID: 8164637). It is primarily recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which play a crucial role in the endogenous immune response against melanoma. Because MART-1 is a lineage-specific differentiation antigen highly expressed in most melanomas, it has been extensively utilized in the development of TCR-engineered T-cell (TCR-T) therapies and peptide-based vaccines (Johnson et al., 2009, PMID: 19147751). Bispecific molecules, such as ImmTACs, are also being developed to redirect T cells to this specific pMHC complex on tumor cells. However, since MART-1 is also expressed in healthy melanocytes in the skin, eye, and inner ear, therapeutic targeting can lead to on-target, off-tumor toxicities such as vitiligo, uveitis, and sensorineural hearing loss (Morgan et al., 2006, PMID: 16946076).

Other names

Melan-A peptide-MHC complexMART-1(26-35)/HLA-A*02:01MART-1(27-35)/HLA-A*02:01pMHC complex (MART-1)Melanoma antigen recognized by T cells 1 peptide-HLA-A2 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to the activation of cytotoxic T lymphocytes and subsequent lysis of tumor cells expressing the antigen.