PRAME peptide–HLA-A2 complex

The **PRAME peptide–HLA-A2 complex** is a cell surface molecular complex consisting of a peptide derived from the Preferentially Expressed Antigen in Melanoma (PRAME) protein and the major histocompatibility complex class I molecule HLA-A*02:01 (HLA-A2). PRAME is an intracellular cancer-testis antigen overexpressed in a wide range of cancers, including leukemias, melanomas, and solid tumors, but is largely absent in most normal tissues. After intracellular proteasomal processing, specific PRAME-derived peptides (such as the 10-mer "ALY" peptide or others) are presented on the cell surface by HLA-A2. This peptide–MHC complex can be recognized by cytotoxic T lymphocytes (CTLs) or by engineered T cell receptors and TCR-mimic antibodies, enabling immune-mediated targeting of tumor cells presenting the complex. Successful presentation of the complex depends on both high PRAME expression and proper antigen processing machinery, particularly the immunoproteasome. The complex is a validated immunotherapeutic target for both cellular therapies (such as TCR-T, TCR-mimic antibodies) and cancer vaccines. Its display is highly cancer-specific, thus supporting development of therapies with limited risk of targeting healthy tissues, though restriction to HLA-A2-positive patients and variable expression across tumor types are notable challenges.

Other names

PRAME–HLA-A2 complexPRAME antigen peptide–HLA-A*02:01 complexPRAME-derived peptide–HLA-A2 complex

Immune targeting of tumor cells via recognition of PRAME peptide presented by HLA-A2 on tumor cell surface, mediating cytotoxicity by CTLs or redirected by antibodies/TCR mimetics. TCR mimic antibodies bind and mediate antibody-dependent cellular cytotoxicity (ADCC)