Melanoma-associated antigen peptide-MHC class I complexes (Melanoma pMHC complexes)

Melanoma-associated antigen peptide-MHC class I complexes are molecular assemblies found on the surface of melanoma cells, consisting of short peptide fragments derived from melanocyte-specific proteins—tyrosinase, MART-1 (Melan-A), and PMEL (gp100)—bound to Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 [1, 6]. These complexes function as the primary ligands for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, enabling the immune system to identify and eliminate malignant melanocytes [2, 11]. In clinical oncology, these pMHC complexes are exploited as therapeutic targets for advanced immunotherapies, such as the bispecific T-cell engager tebentafusp, which specifically targets the gp100-HLA-A*02:01 complex, and various TCR-engineered T-cell (TCR-T) therapies [3, 5]. Because the constituent proteins are differentiation antigens also expressed in healthy melanocytes, therapeutic targeting often results in on-target, off-tumor effects, most notably vitiligo and skin rashes [1, 11]. The efficacy of these treatments is strictly restricted by the patient's HLA type and the presence of the specific antigen within the tumor microenvironment [3, 12].

Other names

Melanocyte differentiation antigen peptide-MHC complexesTyrosinase/MART-1/gp100-HLA complexesgp100/MART-1/Tyrosinase-HLA-A2 complexesMelanoma-associated antigen pMHCs

T-cell redirection and activation via TCR-peptide-MHC interaction