JC polyomavirus VP1 capsid protein-derived peptide–HLA complexes (JCV VP1-HLA complex)

The JC polyomavirus (JCPyV) VP1 capsid protein-derived peptide–HLA complex is a molecular assembly formed by the presentation of viral epitopes on the surface of infected cells or professional antigen-presenting cells (Mani et al., 2016). The VP1 protein is the major structural component of the JCPyV capsid and contains several immunodominant epitopes, such as VP1(100-108), which are presented by specific Human Leukocyte Antigen (HLA) alleles like HLA-A*02:01 (Gupta et al., 2024). This complex serves as the primary recognition site for the host's cellular immune system, specifically cytotoxic T lymphocytes (CTLs) expressing cognate T-cell receptors (TCRs). In patients with Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease caused by JCPyV reactivation, the natural T-cell response is often deficient or exhausted (Jelcic et al., 2015). Therapeutic strategies targeting this complex include the adoptive transfer of virus-specific T cells (VSTs) and engineered TCR-T cell therapies designed to restore immune surveillance and eliminate JCV-infected glial cells (Cellevolve Bio, 2022; AlloVir, 2023). The formation of these complexes is essential for the immune system to distinguish between healthy and infected cells in the central nervous system. By specifically targeting these viral-peptide-loaded HLA molecules, therapies aim to provide a precise cytotoxic response while minimizing damage to healthy brain tissue.

Other names

JCV VP1 peptide-MHC complexJCV VP1 pMHCJC virus VP1 epitope-HLA complexHLA-restricted JCV VP1 peptideJCV VP1-HLA-A*02:01 complexJCPyV VP1-HLA complex

Recognition of the peptide-HLA complex by T-cell receptors (TCRs) on cytotoxic T lymphocytes, triggering the release of perforins and granzymes to induce apoptosis in JC virus-infected cells.