PHOX2B peptide–MHC class I complex

The **PHOX2B peptide–MHC class I complex** refers to a molecular complex in which a short antigenic peptide derived from the PHOX2B protein—a transcription factor aberrantly expressed in neuroblastoma—binds in the peptide-binding groove of a major histocompatibility complex (MHC) class I molecule, notably HLA-A*24:02[1][2][4][6]. This complex is presented on the surface of cancer cells and can be recognized by T cell receptors (TCRs) or engineered synthetic receptors (such as peptide-centric CARs), which then mediate cytotoxic immune responses. Targeting the PHOX2B peptide–MHC class I complex allows for selective immunotherapeutic attack on cancer cells expressing this complex, with recent technologies focusing on engineered CAR T cells (PC-CARs like 10LH) that specifically bind to the peptide-MHC surface for precision therapy in neuroblastoma[1][2][4][7]. However, the specificity of such biologics must be carefully validated to minimize cross-reactivity with complexes on normal tissues to prevent toxicity[4][6].

Other names

PHOX2B/HLA-A*24:02 complexPHOX2B–HLA class I complexPHOX2B pMHC complex

Recognition and killing by peptide-centric chimeric antigen receptor (CAR) T cells or engineered binders that specifically recognize the PHOX2B peptide presented by MHC class I (such as HLA-A*24:02) on cancer cells[1][2][4][7]