Wilms' tumor 1 peptide-HLA complex (WT1-pMHC) (WT1-pMHC)

The Wilms' tumor 1 (WT1) peptide-HLA complex is a molecular target consisting of short peptide fragments derived from the WT1 protein presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (PMID: 17478493). WT1 is a zinc-finger transcription factor that is highly overexpressed in a wide range of hematological malignancies, such as acute myeloid leukemia, and various solid tumors, while maintaining limited expression in normal adult tissues (UniProt P19544). These pMHC complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, triggering an immune response against the cancer cell (PMID: 23486771). Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, TCR-engineered T-cell therapies (TCR-T), and TCR-like antibodies such as ESK1 (PMID: 23486771, ClinicalTrials.gov NCT04056494). Because WT1 is an intracellular protein, the pMHC complex is the primary way the immune system can detect its presence, making it a critical target for precision immunotherapy (PMID: 26034289). The specificity of the interaction depends on both the peptide sequence (e.g., RMFPNAPYL) and the specific HLA allele (e.g., HLA-A*02:01) (PMID: 10833477). Clinical development focuses on maximizing the affinity of the TCR for the pMHC while minimizing cross-reactivity with similar peptides in healthy tissues (PMID: 28677118). Monitoring WT1 expression and HLA status is essential for patient selection in these targeted therapies (PMID: 21406725).

Other names

WT1-MHC complexWT1-HLA complexWilms tumor protein 1 peptide-MHCWT1 antigen-MHC complexWT1-derived peptide-MHC

Recognition by T-cell receptors (TCRs) or TCR-like antibodies leading to targeted lysis of WT1-expressing cells via cytotoxic T-lymphocyte activity or antibody-dependent mechanisms.