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The HLA-A*02:01–PRAME peptide complex is a molecular complex formed by the presentation of a peptide derived from the Preferentially Expressed Antigen in Melanoma (PRAME) protein by the HLA-A*02:01 molecule, a specific variant of the human major histocompatibility complex class I (MHC I)[1][4][6]. PRAME is a cancer-testis antigen highly expressed in various cancers and normally absent or expressed at very low levels in normal tissues[1]. Intracellular processing of PRAME protein leads to generation of specific peptides (notably SLLQHLIGL or similar sequences), which are then loaded onto HLA-A*02:01 and presented on the surface of tumor cells[4][6]. This complex is recognized by cytotoxic T lymphocytes or engineered therapeutics such as TCR-T cells or TCR-mimic antibodies, enabling selective targeting and destruction of PRAME-expressing cancer cells[5][6]. Its restricted presentation makes it an attractive and actively pursued therapeutic target, particularly for immunotherapy of cancers like leukemia and synovial sarcoma[1][5][6]. However, its application is limited by the requirement for both PRAME and HLA-A*02:01 co-expression and concerns regarding immune-mediated toxicity in non-tumor tissues expressing PRAME[5][6].
Recognition by T cells or TCR-mimic antibodies leads to targeted killing of PRAME-expressing tumor cells via cytotoxic T lymphocyte activity in an HLA-A*02:01–restricted manner[1][5][6].
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