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

The HLA-A*02:01-PRAME peptide complex is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 molecule presenting a peptide derived from the Preferentially Expressed Antigen in Melanoma (PRAME) protein, most commonly the SLLMWITQC epitope (PubMed: 15958671). PRAME is a member of the cancer-testis antigen (CTA) family, which is characterized by high expression in various malignancies—including melanoma, sarcoma, and leukemias—while maintaining highly restricted expression in normal adult tissues, primarily the testes and ovaries (UniProt P78395). This restricted expression profile makes the HLA-A2-PRAME complex an attractive therapeutic target for T-cell receptor (TCR)-based interventions, such as TCR-engineered T cells (TCR-T) and bispecific TCR molecules known as ImmTACs (PubMed: 28213372). These therapies are engineered to recognize the pMHC with high affinity and specificity, bypassing the limitations of traditional antibody-based therapies that cannot target intracellular proteins. Clinical-stage candidates like IMA203 and IMC-F106C are currently being evaluated for their ability to induce potent anti-tumor responses in patients whose tumors present this specific antigen complex (Immatics, 2023; Immunocore, 2023). The success of these therapies depends on both the presence of the HLA-A*02:01 allele and the sufficient expression of the PRAME protein within the tumor microenvironment.

Other names

PRAME-HLA-A*02:01 complexSLLMWITQC-HLA-A*02:01 complexHLA-A2-presented PRAME antigenPRAME pMHC

T-cell receptor (TCR) mediated recognition of the specific peptide-MHC complex on the tumor cell surface, leading to T-cell activation, secretion of cytotoxic cytokines, and direct lysis of the target cell.