HLA-A*02:01-tyrosinase peptide complex (HLA-A2-Tyr) (HLA-A2-Tyr)

The HLA-A*0201–tyrosinase peptide complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of melanoma cells and dendritic cells (Wolfel et al., 1994, PMID: 8144862). It consists of the HLA-A*02:01 MHC Class I molecule and a processed peptide fragment derived from tyrosinase, a rate-limiting enzyme in melanin biosynthesis. This complex is a critical target for cancer immunotherapy because tyrosinase is overexpressed in the majority of malignant melanomas (Brichard et al., 1993, PMID: 8404653). Recognition of this pMHC by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes triggers the release of perforins and granzymes, leading to the lysis of the melanoma cell. On dendritic cells, the complex plays a vital role in the cross-presentation and priming of tyrosinase-specific T cells within the lymph nodes. Therapeutic interventions targeting this complex include peptide-based vaccines, TCR-engineered T-cell therapies, and bispecific molecules like ImmTACs such as IMC-F10V (Immunocore, 2024). A significant challenge in targeting this complex is the potential for on-target, off-tumor toxicity, as tyrosinase is also expressed in normal melanocytes in the skin, eyes, and inner ear. Consequently, clinical responses are often associated with autoimmune side effects such as vitiligo or uveitis (Houghton et al., 2001, PMID: 11060339).

Other names

HLA-A*02:01/Tyrosinase(369-377)HLA-A2-Tyr369Tyrosinase-derived peptide-MHC complexHLA-A*02:01-tyrosinase(369-377) complex

T-cell receptor (TCR) binding and activation of CD8+ cytotoxic T lymphocytes, leading to targeted cell lysis via the release of cytotoxic granules like perforin and granzyme.