Human polyomavirus 2 Large T antigen-derived peptides presented on Human Leukocyte Antigen (HLA) (JCV LTAg-HLA complex)

The Human polyomavirus 2 (JC virus) Large T antigen (LTAg) is a multifunctional regulatory protein that is indispensable for viral DNA replication and the activation of late gene expression (Source: UniProt P03070). In infected cells, such as oligodendrocytes and astrocytes, LTAg is processed into short peptide fragments and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, most notably HLA-A*02:01 (Source: Jelcic et al., 2015, Science Translational Medicine). This peptide-MHC complex acts as a critical recognition signal for CD8+ cytotoxic T lymphocytes, which are essential for maintaining the virus in a latent state and preventing the development of Progressive Multifocal Leukoencephalopathy (PML). PML is a devastating demyelinating disease of the central nervous system that arises when JCV reactivates in immunocompromised patients, leading to widespread destruction of glial cells (Source: Cortese et al., 2021, Nature Reviews Neurology). Therapeutic approaches targeting this complex primarily involve adoptive immunotherapy, such as the infusion of ex vivo expanded virus-specific T cells (VSTs) or the use of TCR-engineered T cells designed to specifically lyse JCV-infected cells (Source: Muftuoglu et al., 2018, N Engl J Med). These strategies aim to restore the cellular immune response and are currently being evaluated in clinical settings to improve the prognosis of patients with PML.

Other names

JC virus Large T antigen peptidesJCV LTAg pMHC complexHuman polyomavirus 2 LTAg-HLA complexJCV LTAg epitopesJCV Large T antigen-derived peptides

T-cell mediated cytotoxicity