Target intelligence / Profile preview

Human polyomavirus 2 (JC virus) peptide-MHC class I complex (JCV pMHC-I)

Target
JCV pMHC-I
Molecular classification
Antigen-MHC complex, Viral protein
01

Overview

Human polyomavirus 2 (HPyV-2), commonly known as the JC virus (JCV), is a ubiquitous pathogen that remains latent in the majority of the adult population [PubMed: 31534014]. In severely immunocompromised individuals, such as those with HIV/AIDS or those receiving certain monoclonal antibody therapies, the virus can reactivate and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system [PubMed: 21835161]. The HPyV-2 peptide-MHC class I complex serves as the primary target for the host's cellular immune response, specifically CD8+ cytotoxic T lymphocytes. These complexes consist of viral protein fragments, such as those derived from the Large T antigen or VP1 capsid protein, presented on the surface of infected glial cells by Major Histocompatibility Complex (MHC) class I molecules [PubMed: 29021157]. Therapeutic strategies targeting these complexes include the infusion of ex vivo expanded virus-specific T cells (VSTs) or the development of TCR-engineered T cells designed to recognize specific JCV epitopes. By enhancing the recognition of these pMHC complexes, these therapies aim to restore immune surveillance and clear the viral infection from the brain. However, a significant challenge is the risk of Immune Reconstitution Inflammatory Syndrome (IRIS), where a robust immune response causes life-threatening inflammation in the central nervous system [PubMed: 30305317].

Other names
JC virus peptide-HLA complexHPyV-2 MHC-I restricted antigensJCV T-cell epitopesJCV-specific peptide-MHCHPyV-2 pMHC
02

Mechanism of action

Recognition by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering the release of perforin and granzymes to induce apoptosis in the infected cell.

03

Biological functions

Antigen presentationImmune recognitionT-cell activation
04

Disease associations

Progressive multifocal leukoencephalopathyInfection
05

Safety considerations

Immune Reconstitution Inflammatory Syndrome (IRIS)Off-target T-cell reactivityMHC downregulation by virus
06

Interacting drugs

Virus-specific T cells

1 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeJCV DNA in cerebrospinal fluidJCV-specific T-cell counts

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