Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting tyrosinase (1-9) peptide (HLA-A*02:01/TYR(1-9))

The Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting tyrosinase (1-9) peptide is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical therapeutic target for melanoma. The peptide, consisting of the amino acid sequence MLLAVLYCL, is derived from the signal sequence of the tyrosinase enzyme, which is essential for melanin biosynthesis (Wolfel et al., 1994, Eur J Immunol). In individuals who are HLA-A*02:01 positive, this peptide is processed and displayed on the cell surface, where it can be recognized by the immune system's T-cell receptors (TCRs). Because tyrosinase is highly overexpressed in malignant melanoma cells, this pMHC is targeted by engineered T-cell therapies and bispecific molecules like IMC-tyr to induce tumor-specific lysis (Hassan et al., 2016, J Immunother Cancer). However, since tyrosinase is also expressed in normal melanocytes, targeting this complex can lead to on-target off-tumor toxicities, such as the destruction of healthy pigment cells resulting in vitiligo or uveitis. Clinical success depends on the high-affinity recognition of this complex by therapeutic agents while minimizing cross-reactivity with other self-peptides.

Other names

HLA-A*02:01/MLLAVLYCLTyrosinase 1-9/HLA-A2 complexTYR(1-9)-HLA-A*02:01Melanoma-associated antigen tyrosinase peptide 1-9HLA-A2-restricted tyrosinase epitope

T-cell receptor (TCR) mediated recognition leading to cytotoxic T-lymphocyte activation and tumor cell lysis.