Tyrosinase-derived peptide–Major Histocompatibility Complex (Tyr-pMHC) (Tyr-pMHC)

Tyrosinase-derived peptide–Major Histocompatibility Complex (MHC) complexes are specialized molecular structures formed when fragments of the tyrosinase enzyme are processed and presented on the cell surface by MHC Class I molecules, most commonly HLA-A*02:01 (Brichard et al., 1993, PMID: 8358712). Tyrosinase is the rate-limiting enzyme in melanin biosynthesis and is significantly overexpressed in melanoma, making its peptide-MHC complexes valuable tumor-associated antigens for immunotherapy (Wolfel et al., 1994, PMID: 7524394). These complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which triggers an immune response against the presenting malignant cells. Therapeutic strategies targeting these complexes include the development of TCR-engineered T cells (TCR-T) and bispecific TCR molecules, such as IMC-tyr, which bridge T cells to tumor cells (Immunocore, NCT04112459). However, because tyrosinase is also expressed in healthy melanocytes in the skin, eyes, and inner ear, targeting these complexes can lead to autoimmune-like side effects such as vitiligo, uveitis, or hearing loss (Hassanein et al., 2016, PMID: 27103434). Clinical efficacy is highly dependent on the density of the peptide-MHC complex on the tumor surface and the specificity of the therapeutic TCR.

Other names

Tyrosinase-derived peptide-HLA complexTyr-HLA-A*02:01Tyrosinase antigen-MHC complexpMHC complex (Tyrosinase)Tyrosinase-derived peptide presented by MHC

Recognition of the peptide-MHC complex by engineered or endogenous T-cell receptors (TCRs) induces T-cell activation, cytokine release, and cytotoxic lysis of the target cell.