HLA-A*02:01-restricted PRAME peptide (VLDGLDVLL) complex (HLA-A*02:01/PRAME(100-108))

The HLA-A*02:01 / PRAME_100–108 peptide–HLA complex is a specific molecular target consisting of the Human Leukocyte Antigen (HLA) allele A*02:01 and a 9-amino acid peptide (VLDGLDVLL) derived from the Preferentially Expressed Antigen in Melanoma (PRAME) protein (PMID: 15843433). PRAME is a member of the cancer-testis antigen (CTA) family, which is highly expressed in a wide range of solid and hematological malignancies but has limited expression in normal adult tissues, primarily the testis (PMID: 10360837). This differential expression makes the peptide-MHC complex an ideal target for T-cell receptor (TCR)-based immunotherapies, including TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers (PMID: 32814744). Drugs targeting this complex, such as IMA203 and IMC-F106C, are designed to recognize the specific spatial and chemical configuration of the peptide nestled within the HLA groove (Immatics, 2024; Immunocore, 2024). Upon binding, these therapies trigger a potent cytotoxic immune response against the tumor cell, leading to cell death and potential tumor regression. The complex serves as a critical bridge between the intracellular proteome of the cancer cell and the extracellular recognition machinery of the immune system.

Other names

PRAME-A2 complexHLA-A*02:01/PRAME_VLDGLDVLLPRAME p100-108/HLA-A*02:01Preferentially expressed antigen in melanoma peptide 100-108 presented by HLA-A*02:01

Recognition by engineered T-cell receptors (TCRs) or bispecific TCR-based molecules to induce T-cell mediated lysis of tumor cells.