BK polyomavirus major capsid protein VP1 peptide–MHC complex (BKV VP1-pMHC) (BKV VP1-pMHC)

BK polyomavirus (BKV) is a double-stranded DNA virus that remains latent in the urinary tract of most healthy individuals but can reactivate under immunosuppression, leading to BK virus-associated nephropathy (BKVAN) or hemorrhagic cystitis (PubMed: 18490718). The major capsid protein VP1 is the most abundant structural protein of the virus and serves as a critical target for the host's cellular immune system (UniProt: P03088). In infected cells, VP1 is proteolytically processed into peptides that are subsequently loaded onto Major Histocompatibility Complex (MHC) Class I molecules and displayed on the cell surface (PubMed: 24944288). These VP1 peptide–MHC complexes are the specific ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which mediate the clearance of virally infected cells. Therapeutic strategies targeting these complexes include the adoptive transfer of BKV-specific T cells (e.g., posoleucel) or the development of TCR-engineered T cells to restore viral control and prevent complications in transplant recipients (Allovir; ClinicalTrials.gov: NCT04390113). The efficacy of these therapies depends on the precise recognition of the peptide-MHC complex, making HLA typing a critical component of patient selection. Challenges in targeting these complexes include viral mechanisms of immune evasion, such as the downregulation of MHC molecules, and the potential for off-target cross-reactivity with self-peptides.

Other names

BKV VP1-HLA complexBK polyomavirus VP1-pMHCVP1 peptide-MHC Class I complexBK virus VP1 antigen-MHC complex

T-cell receptor (TCR) binding to the peptide-MHC complex leading to cytotoxic T-cell activation and lysis of infected cells.