Wilms tumor protein 1 peptide 126-134 (RMFPNAPYL) bound to human leukocyte antigen-A*02:01 (WT1₁₂₆/HLA-A*02:01)

The Wilms tumor protein 1 peptide 126-134 (RMFPNAPYL) bound to HLA-A*02:01 is a cancer immunotherapy target consisting of a 9-amino acid epitope derived from the WT1 protein presented on the surface of cells via MHC class I molecules. WT1 is overexpressed in numerous cancers, including acute myeloid leukemia and solid tumors, making this peptide/MHC complex a promising target for therapeutic cancer vaccines. The complex presents a fixed molecular interface recognized by CD8+ T cell receptors, enabling T cells to identify and eliminate WT1-expressing cancer cells. Structural studies have identified an engineered R1Y variant of this peptide that exhibits enhanced binding affinity to HLA-A*02:01 and improved immunogenicity compared to the native peptide, with this variant undergoing clinical evaluation in polyvalent AML vaccines. The therapeutic approach leverages the ability of peptide-based vaccines and TCR-like antibodies to specifically target this cancer-associated epitope while minimizing effects on normal tissues expressing WT1 at physiological levels.

Other names

WT1₁₂₆ epitopeWT1₁₂₆-HLA-A2 complexWT1 peptide/MHC class I complexRMFPNAPYL/HLA-A*0201 complex

The WT1 peptide/HLA-A2 complex is recognized by T cell receptors on CD8+ T cells, triggering T cell activation. Therapeutic approaches include vaccine-induced immunity to stimulate CD8+ T cell responses capable of lysing WT1-expressing leukemic cells, and TCR-like antibody targeting which recognizes the complex as a fixed molecular target, contacting either the peptide directly or specific MHC conformations.