Melanocyte protein PMEL (gp100) peptide 154-162 presented by HLA-A*02:01 (gp100:154-162/HLA-A*02:01)

The gp100:154-162 peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target found on the surface of melanoma cells (PMID: 34551229). The peptide is derived from the melanocyte-specific protein PMEL (also known as gp100), which is involved in melanosome biogenesis (UniProt: P40967). The specific nonamer sequence KTWGQYWQV (residues 154-162) is processed and presented by the HLA-A*02:01 allele, making it a target for T-cell receptor (TCR) based therapies. This complex is the primary target for tebentafusp-tebn (Kimmtrak), the first FDA-approved TCR therapeutic, which is a bispecific fusion protein that redirects T cells to gp100-positive cells (FDA Label: Kimmtrak). While highly effective in uveal melanoma, the target's presence on normal melanocytes in the skin and eye can lead to on-target, off-tumor toxicities such as rash and pruritus (PMID: 35235754). This target represents a significant advancement in TCR-based therapeutics for solid tumors by allowing the immune system to recognize intracellular proteins presented on the cell surface.

Other names

gp100(154-162)PMEL(154-162)KTWGQYWQV peptidegp100-HLA-A*02:01 complexMelanocyte protein PMEL peptide 154-162gp100:154-162 pMHC

T-cell redirection via a bispecific T-cell receptor (TCR) fusion protein (ImmTAC) that binds the pMHC complex and the CD3 epsilon chain on T cells.