Piwi-like protein 1 peptide–HLA-A*02:01 complex (PIWIL1-HLA-A*02:01)

The Piwi-like protein 1 (PIWIL1) peptide–HLA-A*02:01 complex is a specific antigen-presenting structure found on the surface of certain cancer cells. PIWIL1, also known as HIWI, is a member of the Argonaute family that plays a crucial role in the piRNA pathway and is typically expressed only in germline cells (He et al., 2020, Journal of Hematology & Oncology). However, it is frequently re-expressed in various cancers, including gastric, colorectal, and lung cancers, making it a prominent Cancer-Testis Antigen (CTA) (Li et al., 2010, Cardiovascular & Hematological Agents in Medicinal Chemistry). In these malignant cells, PIWIL1 protein is processed into short peptides, such as the HLA-A*02:01-restricted epitope LLVPFVPKV, which are then presented by the MHC Class I molecule HLA-A*02:01 (Xie et al., 2018, OncoTargets and Therapy). This complex is a primary target for immunotherapy, particularly for T-cell receptor (TCR) engineered T-cell therapies and cancer vaccines, because it allows the immune system to distinguish tumor cells from normal somatic tissues. By targeting this specific peptide-MHC complex, therapies aim to trigger a potent cytotoxic T-lymphocyte response that selectively destroys PIWIL1-positive tumor cells while sparing healthy tissue (Wang et al., 2021, Frontiers in Oncology).

Other names

PIWIL1-HLA-A2 complexHIWI-HLA-A*02:01 complexPiwi-like protein 1-MHC class I complexPIWIL1-pMHC

The mechanism involves the high-affinity binding of a therapeutic T-cell receptor (TCR) or TCR-like antibody to the PIWIL1 peptide presented within the HLA-A*02:01 groove, which triggers the formation of an immunological synapse and subsequent release of perforins and granzymes to induce apoptosis in the target cell.