Tyrosinase-HLA-A*02:01 peptide-MHC complex (TYR-HLA-A*02:01 pMHC)

The tyrosinase-HLA-A*02:01 peptide-MHC complex is a specific molecular target found on the surface of melanoma cells, consisting of a peptide fragment derived from the tyrosinase enzyme presented by the Human Leukocyte Antigen (HLA) allele A*02:01 (Wolfel et al., 1994). Tyrosinase is a key enzyme in melanin biosynthesis and is highly expressed in both malignant melanoma and normal melanocytes (UniProt P14679). This complex serves as a crucial recognition site for the immune system, specifically for T-cell receptors (TCRs) that can distinguish cancer cells from most healthy tissues. Therapeutic strategies targeting this complex include T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific molecules like ImmTACs (Immune mobilizing monoclonal TCRs against cancer) (Immunocore, 2023). The most common peptide epitope involved is the nonapeptide YMDGTMSQV, which often results from the post-translational deamidation of an asparagine residue (Skipper et al., 1996). Because tyrosinase is also expressed in healthy melanocytes, treatment can lead to on-target, off-tumor effects such as vitiligo or uveitis. Despite these challenges, the high specificity of the pMHC complex makes it an attractive target for precision immunotherapy in HLA-A*02:01-positive melanoma patients.

Other names

Tyrosinase peptide-HLA-A*02:01 complexTYR:HLA-A*02:01Tyrosinase(369-377)-HLA-A*02:01YMDGTMSQV-HLA-A*02:01

T-cell receptor (TCR) mediated recognition and subsequent T-cell activation leading to target cell lysis.