JC polyomavirus large T antigen-derived peptides presented by HLA class I molecules (JCV LTAg-HLA-I)

The JC polyomavirus (JCV) large T antigen (LTAg) is a regulatory protein required for viral DNA replication and the orchestration of the viral life cycle (UniProt P03072). In the context of immunosuppression, JCV can reactivate and cause Progressive Multifocal Leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system (Koralnik, 2006, J. Infect. Dis.). Peptides derived from the LTAg are processed intracellularly and presented on the cell surface by patient-specific HLA class I molecules (Du Pasquier et al., 2003, J. Virol.). These peptide-HLA complexes are the cognate targets for CD8+ cytotoxic T lymphocytes, which play a decisive role in controlling JCV infection and preventing PML progression (Saburi et al., 2011, J. Virol.). Therapeutic interventions targeting these complexes include the adoptive transfer of JCV-specific T cells (VSTs) derived from healthy donors or the patient's own repertoire (Muftuoglu et al., 2018, N. Engl. J. Med.). Additionally, research into T-cell receptor (TCR) therapies focuses on engineering T cells to specifically recognize these LTAg-HLA complexes to restore anti-viral immunity (Lambert et al., 2022, Front. Immunol.). The presence and magnitude of the T-cell response against these specific epitopes are often used as prognostic indicators in patients at risk for or suffering from PML (Lima et al., 2010, Clin. Infect. Dis.).

Other names

JCV large T antigen peptidesJCV LTAg epitopesHLA-restricted JCV LTAg peptidesJCV LTAg-MHC class I complex

Targeted lysis of JCV-infected cells via CD8+ T-cell recognition of peptide-MHC complexes