Tyrosinase peptide-MHC complex (TYR-pMHC)

The Tyrosinase peptide-MHC complex is a tumor-associated antigen (TAA) target primarily used in the development of adoptive T-cell therapies for melanoma. Tyrosinase is a key enzyme in melanin biosynthesis, and its expression is highly restricted to melanocytes and melanoma cells. Specific peptides derived from tyrosinase, such as the HLA-A*02:01-restricted epitope (e.g., YMDGTMSQV), are presented on the cell surface by MHC class I molecules. Engineered T-cell receptors (TCRs) are designed to recognize these complexes with high affinity and specificity, enabling the immune system to selectively target and destroy melanoma cells. However, because tyrosinase is also expressed in normal melanocytes, therapies targeting this complex can lead to autoimmune-like toxicities in the skin, eyes, and ears, such as vitiligo and uveitis. Clinical development of TCR-T therapies targeting this complex, such as those utilizing the TIL 1383I TCR, aims to harness the precision of the cellular immune response while managing these predictable side effects.

Other names

Tyrosinase-specific T-cell receptors recognizing tyrosinase-derived peptide–MHC complexesTyrosinase-derived peptide-MHC complexHLA-A*02:01/Tyrosinase(368-376) complexTyrosinase antigenTYR-HLA-A2 complexTyrosinase-specific T-cell receptor target

T-cell receptor-mediated recognition of peptide-MHC complex leading to T-cell activation, cytokine release, and tumor cell lysis