Wilms' tumor 1 peptide–HLA class I complex (WT1-HLA complex) (WT1-HLA complex)

The Wilms' tumor 1 (WT1) peptide–HLA class I complex is a tumor-associated antigen complex presented on the surface of malignant cells and antigen-presenting cells. WT1 is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation; while its expression is low in normal adult tissues, it is highly overexpressed in various leukemias and solid tumors (Source: National Cancer Institute). Intracellular WT1 protein is degraded by the proteasome into short peptides, which are then transported into the endoplasmic reticulum and loaded onto HLA class I molecules for presentation on the cell surface. These peptide-MHC complexes serve as the primary target for CD8+ T-cell recognition via their T-cell receptors (TCRs). Therapeutic interventions targeting these complexes include peptide vaccines designed to elicit endogenous T-cell responses, as well as adoptive cell therapies like TCR-engineered T cells (TCR-T) and TCR-like antibodies that can bind the complex with high specificity (Source: Journal of Hematology & Oncology). This target is particularly valuable because it allows for the targeting of an intracellular oncogenic protein that is otherwise "undruggable" by conventional monoclonal antibodies.

Other names

WT1-MHC class I complexWT1 peptide-MHCWT1-pMHCWilms' tumor 1 antigen-HLA complex

Recognition of the peptide-HLA complex by T-cell receptors (TCRs) or TCR-like antibodies, which triggers an immune response, specifically the activation of cytotoxic T lymphocytes (CTLs) to induce apoptosis in cells presenting the WT1 antigen.