Tyrosinase peptide–Major Histocompatibility Complex class I complex (Tyr-MHC complex)

The Tyrosinase peptide–Major Histocompatibility Complex (MHC) class I complex is a specific molecular assembly found on the surface of melanoma cells, consisting of a peptide fragment derived from the tyrosinase enzyme bound to an MHC class I molecule, most commonly HLA-A*02:01 [PMID: 8144862]. Tyrosinase is a copper-containing enzyme essential for melanin biosynthesis and is highly expressed in both cutaneous and uveal melanoma, making its processed peptides significant tumor-associated antigens [UniProt P14679]. This complex serves as a critical ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, which recognize the specific peptide-MHC configuration to initiate an immune response against the tumor [PMID: 15155838]. In clinical development, this target is addressed by various immunotherapies, including bispecific T-cell engagers like GSK3377794 (IMC-tyr) and TCR-engineered T-cell therapies, which aim to redirect the immune system to kill cells presenting this complex [PMID: 30104351]. Because tyrosinase is also expressed in healthy melanocytes in the skin, eyes, and inner ear, therapeutic targeting of this complex carries risks of on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss [PMID: 26903545]. Consequently, patient selection often requires screening for both the specific HLA genotype and the presence of tyrosinase expression within the tumor.

Other names

Tyrosinase-derived peptide-HLA complexHLA-A*02:01/Tyrosinase(369-377) complexTyrosinase-MHC I complexTyr-HLA-A2 complexTyrosinase-derived epitope

T-cell receptor (TCR) binding to the peptide-MHC complex on tumor cells, triggering cytotoxic T-lymphocyte activation and tumor cell lysis.