HLA-A*02:01-Wilms' tumor 1 (WT1) heteroclitic peptide complex (HLA-A*02:01/WT1)

The HLA-A*02:01 presenting WT1-derived heteroclitic peptide is a peptide-major histocompatibility complex (pMHC) that serves as a specific target for cancer immunotherapy. Wilms' Tumor 1 (WT1) is a zinc-finger transcription factor that is highly overexpressed in a wide range of leukemias and solid tumors, while maintaining very limited expression in healthy adult tissues (Cheever et al., 2009, Clinical Cancer Research). Heteroclitic peptides are synthetic variants of native tumor-associated antigens, modified—typically at the HLA anchor residues—to increase their binding affinity and stability when presented by HLA-A*02:01 (Pinilla-Ibarz et al., 2000, Leukemia). This enhanced stability facilitates a more robust activation of the immune system, particularly cytotoxic T lymphocytes (CTLs), compared to the native peptide sequence. Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, TCR-engineered T-cell therapies, and TCR-mimetic antibodies designed to recognize the specific pMHC configuration (Maslak et al., 2018, Blood Advances). By focusing on this complex, clinicians aim to direct the patient's immune system to selectively identify and eliminate WT1-expressing malignant cells.

Other names

HLA-A*02:01/WT1(126-134) analogWT1-A2 complexYMFPNAPYL/HLA-A*02:01WT1 heteroclitic peptide-MHC complex

The mechanism involves the specific recognition of the HLA-A*02:01/WT1 peptide complex by T-cell receptors (TCRs) on the surface of CD8+ T cells, leading to T-cell activation, proliferation, and the subsequent lysis of target tumor cells (Dao et al., 2013, Science Translational Medicine).