Wilms tumor protein-derived epitope presented by HLA-A*02:01 (WT1/HLA-A*02:01)

The Wilms tumor protein-derived epitope presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. The Wilms tumor 1 (WT1) protein is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation; while it is essential during embryonic development, its expression is highly restricted in healthy adult tissues but significantly overexpressed in various cancers (Cheever et al., 2009, Clinical Cancer Research). The specific nonamer peptide RMFPNAPYL (residues 126-134) is one of the most immunogenic epitopes of WT1 and is presented on the cell surface by the HLA-A*02:01 allele (Oka et al., 2000, Immunogenetics). This complex serves as a target for several therapeutic modalities, including TCR-engineered T-cells (TCR-T), TCR-like antibodies, and peptide vaccines like Galinpepimut-S (Maslak et al., 2018, Blood Advances). By targeting this pMHC, therapies aim to induce a cytotoxic T-lymphocyte response specifically against malignant cells in diseases such as acute myeloid leukemia (AML) and mesothelioma.

Other names

WT1(126-134)/HLA-A*02:01RMFPNAPYL-HLA-A*02:01 complexWT1-A2 complexWilms tumor 1 peptide-MHC complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to T-cell mediated cytotoxicity and tumor cell lysis.