Wilms' tumor 1 (WT1)-derived peptide epitope presented by HLA-A*02:01 (WT1/HLA-A*02:01)

The Wilms' tumor 1 (WT1) protein is a zinc-finger transcription factor that is highly overexpressed in a variety of hematological malignancies and solid tumors, while maintaining very low expression in normal adult tissues (Cheever et al., 2009, PMID: 19723909). Intracellular WT1 protein is processed by the proteasome into short peptide fragments, which are then transported to the endoplasmic reticulum and loaded onto Major Histocompatibility Complex (MHC) Class I molecules. The specific complex formed by a WT1-derived peptide (such as the RMFPNAPYL or SLGEQQYSV sequences) and the HLA-A*02:01 allele is presented on the cell surface, acting as a "red flag" for the immune system (Oka et al., 2004, PMID: 14710020). This peptide-MHC complex is a primary target for various immunotherapeutic strategies, including TCR-engineered T-cell (TCR-T) therapies, peptide-based vaccines, and TCR-like monoclonal antibodies (Dao et al., 2013, PMID: 23486626). These therapies aim to exploit the differential expression of WT1 to selectively eliminate cancer cells while minimizing damage to healthy tissues.

Other names

WT1-A2 complexWT1 peptide-MHC complexRMFPNAPYL-HLA-A*02:01SLGEQQYSV-HLA-A*02:01WT1(126-134)/HLA-A*02:01WT1(187-195)/HLA-A*02:01

The mechanism involves the recognition of the specific WT1 peptide/HLA-A*02:01 complex by either endogenous T cells (stimulated by vaccines) or engineered T cells (TCR-T), leading to the formation of an immunological synapse and subsequent release of perforins and granzymes to induce apoptosis in the target cell (Schmitt et al., 2013, PMID: 23319793).