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

The Human polyomavirus 2 VP1 capsid protein–derived peptide–HLA complex is a molecular assembly consisting of a specific peptide fragment from the major capsid protein (VP1) of the JC virus (JCV) bound to a Human Leukocyte Antigen (HLA) molecule (UniProt P03089). This complex is presented on the surface of JCV-infected cells, particularly oligodendrocytes and astrocytes in the central nervous system. It serves as a critical recognition element for the host immune system, specifically for CD8+ cytotoxic T lymphocytes (CTLs) via their T-cell receptors (TCRs) (Lima et al., 2010). In patients with Progressive Multifocal Leukoencephalopathy (PML), a debilitating demyelinating disease caused by JCV reactivation, the immune response to this complex is often insufficient or absent due to severe immunosuppression. Therapeutic strategies targeting this complex include the administration of ex vivo expanded virus-specific T-cells (VSTs) or TCR-engineered T-cells designed to recognize the VP1-HLA assembly (Kasten et al., 2021). By enhancing the recognition of this target, these therapies aim to clear the viral infection and halt the progression of PML.

Other names

JC virus VP1 peptide-MHC complexJCV VP1 epitope-HLA complexHuman polyomavirus 2 VP1-HLA complexJCV VP1-HLA-A*02:01 complex

The complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, which triggers the release of perforins and granzymes to induce apoptosis in JC virus-infected cells (Muftuoglu et al., 2018).