Tyrosinase peptide-HLA complex (Tyr-pMHC)

The tyrosinase peptide-HLA complex consists of specific peptide fragments derived from the tyrosinase enzyme, such as the widely studied Tyr369-377 (YMDGTMSQV) epitope, presented on the surface of cells by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01. Tyrosinase is a key enzyme in melanin biosynthesis and is highly expressed in both normal melanocytes and melanoma cells, making these peptide-MHC complexes prime targets for T-cell-based immunotherapies. Recognition of these complexes by endogenous or engineered T-cell receptors (TCRs) triggers a targeted immune response against the presenting cell. (Source: PubMed PMID: 15585850, 21149615). In the context of oncology, this target is utilized for the development of TCR-engineered T-cell therapies (TCR-T) and bispecific TCR molecules, such as ImmTACs, which redirect T-cells to kill melanoma cells. Because tyrosinase is also expressed in healthy melanocytes in the skin and eyes, therapeutic targeting can lead to on-target off-tumor toxicities, including vitiligo and uveitis. Clinical efficacy is often monitored through the presence of the specific HLA allele and the expression levels of tyrosinase within the tumor microenvironment. (Source: ClinicalTrials.gov NCT04102436, Journal of Immunotherapy of Cancer).

Other names

Tyrosinase-derived peptides presented on MHC moleculesTyrosinase-HLA-A*02:01 complexTyrosinase-derived epitopesMelanocyte-differentiation antigen peptidesTyr369-377 peptide-MHC

T-cell receptor (TCR) mediated recognition leading to T-cell activation and cytotoxic lysis of tyrosinase-expressing cells.