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

The HLA-A*02:01-Melan-A (26-35) complex is a major histocompatibility complex (MHC) class I molecule presenting a specific immunodominant epitope derived from the Melan-A (also known as MART-1) protein (7, 15). This complex is a key therapeutic target in melanoma because Melan-A is highly expressed in over 90% of melanoma tumors while being restricted to melanocytes in healthy tissues (12, 21). The 26-35 epitope (EAAGIGILTV) is recognized by an unusually high frequency of CD8+ T cells in HLA-A*02:01-positive individuals, making it an ideal candidate for immunotherapy (7, 10). Current therapeutic approaches include TCR-engineered T-cell (TCR-T) therapies and peptide vaccines, which often utilize a modified heteroclitic peptide (ELAGIGILTV) to enhance binding affinity and T-cell activation (13, 18). However, because Melan-A is also expressed in normal melanocytes, targeting this complex can lead to on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss (12). Despite these challenges, the complex remains a cornerstone of precision oncology for HLA-A*02:01-positive melanoma patients (12, 15).

Other names

MART-1 26-35/HLA-A*02:01Melan-A 26-35/HLA-A*02:01EAAGIGILTV-HLA-A*02:01ELAGIGILTV-HLA-A*02:01MART-1 peptide-MHC complexMelanoma antigen recognized by T cells 1 (26-35) HLA-A2 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the cell surface, leading to T-cell activation, secretion of cytotoxic granules such as perforin and granzyme, and targeted lysis of the antigen-presenting cell (12, 15).