Wilms tumor 1 protein-derived peptide–HLA complex (WT1-HLA complex) (WT1-HLA complex)

The Wilms tumor 1 (WT1) protein-derived peptide–HLA complex is a cell-surface antigen consisting of a processed peptide fragment of the WT1 transcription factor presented by Human Leukocyte Antigen (HLA) molecules (PMID: 17460621). WT1 is a zinc-finger protein that is highly overexpressed in various hematological malignancies and solid tumors, while having limited expression in normal adult tissues, making its peptide-MHC complexes attractive targets for immunotherapy (UniProt: P19544). These complexes are recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, triggering an immune response against the tumor cell. Therapeutic strategies targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, peptide vaccines, and TCR-mimic antibodies or bispecific molecules (PMID: 30610019). Because WT1 is an intracellular protein, the peptide-HLA complex is the primary way the immune system can detect its presence on the cell surface. The clinical application of these therapies is typically restricted to patients with specific HLA alleles, such as HLA-A*02:01 or HLA-A*24:02, which are capable of presenting the immunogenic WT1 peptides.

Other names

WT1-pMHCWT1 peptide-MHC complexWilms tumor protein 1 peptide-HLA complexWT1-HLA-A*02:01 complexWT1-HLA-A*24:02 complex

Recognition of the peptide-HLA complex by T-cell receptors (TCRs) or TCR-mimetic molecules, leading to T-cell activation and targeted lysis of WT1-expressing cells.