HLA-A*02:01-presented gp100 and tyrosinase peptide-MHC complexes (gp100/TYR pMHC)

HLA-A*02:01-presented gp100 and tyrosinase peptide-MHC complexes are specialized molecular targets used in the immunotherapy of malignant melanoma. These complexes consist of immunodominant peptide epitopes derived from the melanocyte-differentiation antigens gp100 (also known as PMEL) and tyrosinase (TYR), which are processed and displayed on the cell surface by the Human Leukocyte Antigen (HLA) A*02:01 molecule (UniProt P40967, P14679). On antigen-presenting cells (APCs), these complexes are essential for the priming and activation of CD8+ cytotoxic T lymphocytes through interaction with the T-cell receptor (TCR). In the context of tumor cells, they serve as the recognition site for therapeutic agents such as Tebentafusp, a bispecific T-cell engager that redirects T cells to eliminate gp100-expressing cells (PMID: 34554117). Because gp100 and tyrosinase are lineage-specific proteins, these targets are highly expressed in melanoma but also present on healthy melanocytes in the skin, eyes, and ears. Consequently, therapies targeting these complexes can lead to autoimmune-like side effects, including vitiligo and uveitis (PMID: 21632993, PMID: 15150568).

Other names

HLA-A2-presented gp100 and tyrosinase peptide epitopesgp100/HLA-A*02:01 complexTyrosinase/HLA-A*02:01 complexPMEL/HLA-A2TYR/HLA-A2Melanoma-associated antigen peptide-MHC complexes

T-cell redirection and activation via TCR-pMHC binding