HLA-A*02:01-presented phosphorylated insulin receptor substrate 2 (1097-1105) epitope (HLA-A*02:01/pIRS2(1097-1105))

The HLA-A*02:01-presented pIRS2(1097-1105) epitope is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various tumor cells. It consists of a nine-amino acid phosphorylated peptide (RVApYASASL) derived from the Insulin Receptor Substrate 2 (IRS2) protein, bound to the HLA-A*02:01 molecule (Cobbold et al., 2013, Science Translational Medicine). IRS2 is a critical component of the insulin and IGF-1 signaling pathways, and its aberrant phosphorylation is frequently observed in cancers such as leukemia, melanoma, and breast cancer (Zarling et al., 2006, Journal of Experimental Medicine). This complex acts as a phosphoneoantigen, allowing the immune system to distinguish malignant cells with dysregulated signaling from healthy cells (Engelhard et al., 2008, Seminars in Immunology). Therapeutic approaches targeting this epitope include TCR-engineered T-cells and TCR-mimic (TCRm) antibodies, which are designed to recognize the unique structural features of the phosphopeptide within the MHC groove (Mohammed et al., 2008, Journal of Biological Chemistry). Because this target is post-translationally modified and tumor-associated, it offers a strategy for immunotherapy that bypasses the need for patient-specific somatic mutations.

Other names

pIRS2(1097-1105) phosphopeptide-MHC complexRVApYASASL/HLA-A*02:01Phospho-IRS2 epitopeIRS2 phosphoneoantigenHLA-A2/pIRS2 epitope

Induction of T-cell mediated cytotoxicity and targeted cell lysis through specific recognition of the phosphopeptide-MHC complex