Preferentially expressed antigen in melanoma (PRAME) peptide–Major Histocompatibility Complex (MHC) class I complex (PRAME-MHC I)

The Preferentially Expressed Antigen in Melanoma (PRAME) peptide–Major Histocompatibility Complex (MHC) class I complex is a specific molecular assembly found on the surface of various malignant cells, serving as a critical target for T-cell-based cancer immunotherapies. PRAME is a member of the cancer-testis antigen (CTA) family, which is characterized by high expression in a wide range of cancers—including melanoma, synovial sarcoma, and certain leukemias—while remaining largely absent from healthy adult tissues, except for immune-privileged sites like the testis (UniProt P78395; PubMed 30552151). Within the tumor cell, PRAME protein is degraded into specific peptides, such as the SLLQHLIGL epitope, which are then loaded onto MHC class I molecules (typically HLA-A*02:01) and presented on the cell surface (PubMed 28213370). This presentation allows the complex to be recognized by engineered T-cell receptors (TCRs) on therapeutic T cells or by bispecific T-cell engagers, triggering a targeted cytotoxic immune response against the tumor (Immatics, IMA203/IMA402). Because PRAME is an intracellular antigen, the peptide-MHC complex is the only way for the immune system to detect its presence, making it a cornerstone for next-generation adoptive cell therapies and TCR-bispecifics. Clinical development of drugs targeting this complex has shown significant potential in treating solid tumors that are refractory to standard checkpoint inhibitors, with patient selection typically requiring both PRAME expression and a specific HLA genotype (PubMed 36109515).

Other names

PRAME-HLA complexPRAME-HLA-A*02:01 complexMAPE-MHC complexMelanoma antigen preferentially expressed peptide-MHC complexPRAME-MHC class I complex

T-cell receptor (TCR) mediated recognition and cytotoxic killing of tumor cells presenting the PRAME peptide-MHC complex.