Melanoma antigen recognized by T cells 1 (27-35) peptide presented by Human Leukocyte Antigen A*02:01 (MART-1(27-35)/HLA-A*02:01)

The MART-1:27-35 peptide presented by Human Leukocyte Antigen (HLA)-A*02:01 is a critical peptide-major histocompatibility complex (pMHC) target in the field of melanoma immunotherapy [1]. MART-1, also known as Melan-A, is a transmembrane protein primarily expressed in melanocytes and is essential for the expression and stability of Pmel17, a protein involved in melanosome maturation [1, 2]. In the context of malignancy, MART-1 is highly overexpressed in over 90% of melanoma cases, making it an ideal tumor-associated antigen [2]. The specific nonameric peptide sequence AAGIGILTV (residues 27-35) is the immunodominant epitope recognized by the majority of HLA-A*02:01-restricted tumor-infiltrating lymphocytes [2, 3]. Therapeutic interventions targeting this pMHC complex include the development of T-cell receptor (TCR) engineered T-cell therapies, such as BPX-701, and various peptide-based vaccines designed to stimulate an endogenous immune response [3, 4]. While these therapies have shown the ability to induce significant tumor regression, they are often associated with on-target, off-tumor toxicities due to the presence of MART-1 in healthy melanocytes located in the skin, eyes, and inner ear [4]. Consequently, patients may experience side effects such as vitiligo, uveitis, and hearing loss during treatment [3, 4]. Despite these safety challenges, the MART-1:27-35/HLA-A*02:01 complex remains a foundational target for validating new modalities in cellular immunotherapy and synthetic immunology.

Other names

Melan-A (27-35)/HLA-A*02:01MART-1(27-35)/HLA-A2AAGIGILTV/HLA-A*02:01 complexMART1-HLA-A2

The target is recognized by engineered or endogenous T-cell receptors (TCRs), which triggers the activation of cytotoxic T lymphocytes (CTLs) to induce apoptosis in cells expressing the MART-1 peptide on HLA-A*02:01 [3, 4].