Human polyomavirus 2 major capsid protein VP1 peptide-HLA complex (JCV VP1-HLA)

Human polyomavirus 2 (JCV) major capsid protein VP1 is the primary structural component of the viral shell and a critical target for the host immune system (UniProt P03089). In patients with Progressive Multifocal Leukoencephalopathy (PML), the virus reactivates and infects oligodendrocytes, leading to severe demyelination (NINDS, 2023). Peptides derived from the VP1 protein are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, such as HLA-A*02:01, which are essential for T-cell recognition (Jelcic et al., 2015, PubMed: 26379289). These peptide-HLA complexes serve as the specific ligands for CD8+ T-cell receptors, triggering a cytotoxic immune response against infected cells (Muftuoglu et al., 2018, PubMed: 30209040). Therapeutic strategies focusing on this target include the use of adoptively transferred virus-specific T cells (VSTs) and engineered TCR-T cell therapies designed to recognize these specific viral epitopes and restore immune control in immunocompromised individuals (AlloVir, 2024; ClinicalTrials.gov NCT04605445). This target is particularly significant in the context of HIV/AIDS and post-transplant immunosuppression where JCV reactivation is most prevalent.

Other names

JC virus VP1 peptide-HLAJCV VP1 pMHCJCV major capsid protein VP1 antigenHuman polyomavirus 2 VP1 peptide-MHC complexJCV VP1-derived peptides presented on MHC

The target complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, which then release cytotoxic granules containing perforin and granzymes to induce apoptosis in the JCV-infected host cell (Muftuoglu et al., 2018, PubMed: 30209040).