Human polyomavirus 2 small t antigen-derived peptides presented on human leukocyte antigen (JCV stAg-HLA complex)

Human polyomavirus 2 (JCV) small t antigen (stAg) is a regulatory protein essential for viral genome replication and the modulation of host cell signaling pathways, primarily through its interaction with protein phosphatase 2A (PP2A) (UniProt: P03072). During infection, stAg is proteolytically processed into short peptides that are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, forming a complex that serves as a critical target for CD8+ cytotoxic T lymphocytes (PubMed: 24965443). This immune recognition is vital for controlling JCV replication, particularly in the central nervous system where the virus can cause Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease (NIH: Progressive Multifocal Leukoencephalopathy). Therapeutic strategies targeting these peptide-HLA complexes include the development of virus-specific T-cell (VST) therapies and TCR-engineered cells designed to restore immune surveillance in immunocompromised patients (PubMed: 30209444). Because these complexes are specific to infected cells, they provide a high-precision target for immunotherapy, although the risk of Immune Reconstitution Inflammatory Syndrome (IRIS) remains a significant clinical concern (PubMed: 20147524).

Other names

JC virus small t antigen-HLA complexJCV stAg peptidesHuman polyomavirus 2 small T-antigenJCV small t antigen-MHC complexJCV stAg-derived epitopes

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the targeted lysis of JC virus-infected cells.