HLA-A*02:01-presented MART-1 (27-35) epitope (HLA-A2/MART-1(27-35))

The HLA-A*02:01-presented MART-1 (27-35) epitope is a major tumor-associated antigen complex used in the development of immunotherapies for melanoma (Kawakami et al., 1994, PNAS). MART-1, or Melan-A, is a protein involved in melanosome biogenesis and is expressed in over 80% of melanoma cases (UniProt Q16655). The specific nonamer peptide AAGIGILTV is processed and presented by the MHC Class I molecule HLA-A*02:01, allowing it to be recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes. Because of its high prevalence and immunogenicity, this complex has been a primary target for TCR-engineered T-cell therapies and peptide-based vaccines (Johnson et al., 2009, Blood). However, MART-1 is also expressed in normal melanocytes found in the skin, eyes, and inner ear, which can lead to on-target, off-tumor toxicities. Clinical trials have observed side effects such as vitiligo, uveitis, and hearing loss in patients receiving MART-1 targeted therapies (Choudhary et al., 2012, Journal of Clinical Oncology). Despite these safety concerns, the epitope remains a critical benchmark for evaluating the efficacy of novel T-cell redirection platforms.

Other names

Melan-A (27-35)MART-1 (27-35)AAGIGILTV peptideHLA-A*02:01/MART-1 complexMelanoma antigen recognized by T cells 1

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