JC polyomavirus peptide–Human Leukocyte Antigen complex (JCV peptide–HLA complex)

JC polyomavirus (JCV) peptide–Human Leukocyte Antigen (HLA) complexes are molecular structures presented on the surface of host cells, such as oligodendrocytes and astrocytes, following infection by the JC virus. These complexes are formed when viral proteins, including the Large T-antigen and VP1 capsid protein, are proteolytically processed into short peptides and loaded onto HLA Class I or II molecules within the endoplasmic reticulum (Koralnik et al., 2001, J. Immunol). The presentation of these viral epitopes is critical for the host's cellular immune response, as they are the specific ligands recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T cells. In patients with impaired cell-mediated immunity, such as those with HIV/AIDS or those receiving immunosuppressive therapies, the lack of effective recognition of these complexes allows for uncontrolled viral replication, leading to Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease (Muftuoglu et al., 2018, NEJM). Therapeutic interventions currently focus on restoring this recognition through the adoptive transfer of ex vivo expanded JCV-specific T cells or the use of immune checkpoint inhibitors like pembrolizumab to enhance the endogenous T-cell response against these complexes (Cortese et al., 2019, N. Engl. J. Med.). A significant therapeutic challenge is the risk of Immune Reconstitution Inflammatory Syndrome (IRIS), where a vigorous immune response against these complexes causes severe inflammatory damage to the central nervous system (Tan et al., 2011, Lancet Neurol).

Other names

JCV-HLA complexJC virus peptide-MHC complexJCV pMHCJCV antigen-HLA complexJCV epitope-HLA complex

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) triggers the activation of cytotoxic T lymphocytes, leading to the targeted lysis of JC virus-infected cells and the secretion of antiviral cytokines.