Human polyomavirus 2 Large T antigen–derived peptide–HLA complex (JCV LTAg-peptide-HLA complex)

The Human polyomavirus 2 (JC virus) Large T antigen-derived peptide-HLA complex is a molecular assembly formed when specific peptide fragments from the viral Large T antigen (LTAg) are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. JC virus (JCV) is the causative agent of Progressive Multifocal Leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system that primarily affects immunocompromised individuals, such as those with HIV/AIDS or patients receiving potent immunosuppressive therapies. The Large T antigen is a multifunctional regulatory protein essential for viral DNA replication and cellular transformation, making its processed peptides primary targets for the host's cellular immune response. Therapeutic strategies targeting this complex include adoptive T-cell therapies, such as viral-specific T cells (VSTs) and T-cell receptor (TCR) engineered T cells, which aim to restore or enhance the immune system's ability to recognize and eliminate JCV-infected cells. Monitoring the presence of specific HLA alleles, particularly HLA-A*02:01, and the magnitude of the LTAg-specific T-cell response is critical for managing PML and predicting treatment outcomes. However, rapid immune restoration against this target can lead to Immune Reconstitution Inflammatory Syndrome (IRIS), a significant therapeutic challenge that can paradoxically worsen neurological symptoms.

Other names

JC virus Large T antigen-peptide-HLA complexJCV LTAg-MHC complexHuman polyomavirus 2 LTAg-HLA complexJCV LTAg-HLA-A*02:01 complex

Recognition by cytotoxic T lymphocytes (CTLs) via T-cell receptors (TCRs), leading to the targeted lysis of virus-infected cells expressing the viral antigen.