JC virus peptide–HLA class I complex (JCV-HLA-I)

JC virus peptide–HLA class I complexes are molecular assemblies presented on the surface of cells infected with the JC polyomavirus (JCV), primarily oligodendrocytes and astrocytes in the central nervous system. These complexes consist of viral-derived peptides, such as those from the VP1 capsid protein or Large T-antigen, bound to the cleft of Human Leukocyte Antigen (HLA) class I molecules (PMID: 20843757). Their primary biological function is to act as ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, facilitating the immune-mediated identification and destruction of virally infected cells. In patients with Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease, the failure of the cellular immune response to recognize these complexes allows for unchecked viral replication and brain tissue destruction (PMID: 30209121). Therapeutic strategies targeting these complexes involve adoptive immunotherapy, such as the infusion of JCV-specific T cells (VSTs) or TCR-engineered T cells designed to bind specifically to these pMHC targets. Clinical management often involves HLA typing and monitoring JCV-specific T-cell frequencies to assess the risk and progression of PML.

Other names

JCV peptide-MHC class I complexJohn Cunningham virus antigen-HLA complexJCV pMHC class IJCV-specific HLA-peptide complex

Recognition by the T-cell receptor (TCR) of CD8+ cytotoxic T cells, triggering the release of perforin and granzymes to induce apoptosis in the infected host cell.