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Human herpesvirus 6 antigen-derived peptide-Human leukocyte antigen complex (HHV-6 peptide-HLA) (HHV-6 peptide-HLA)

Target
HHV-6 peptide-HLA
Molecular classification
MHC-peptide complex, Antigen-presenting complex, Protein complex
01

Overview

Human herpesvirus 6 (HHV-6) antigen-derived peptide-Human leukocyte antigen (HLA) complexes are molecular assemblies consisting of viral protein fragments presented on the surface of host cells by HLA molecules. These complexes are the primary targets for T-cell-mediated immunity, where specific T-cell receptors (TCRs) recognize the combination of the viral peptide and the host HLA to initiate an immune response [PubMed: 31439678]. HHV-6, which includes variants A and B, is a widespread beta-herpesvirus that establishes latency and can reactivate in immunocompromised patients, leading to severe conditions such as encephalitis, myocarditis, and transplant rejection [PubMed: 25535215]. In therapeutic development, these complexes are targeted by adoptive T-cell therapies, such as posoleucel, which utilize donor-derived T cells to restore viral control in patients post-transplant [AlloVir, 2023]. The effectiveness of these therapies depends on the precise matching of the HLA allele and the viral epitope, such as those derived from the U54 or U90 proteins [PubMed: 24109115]. Monitoring these complexes and the corresponding T-cell response is essential for managing viral reactivation and ensuring the safety of cellular immunotherapies. Potential risks include off-target toxicity if the TCR recognizes similar self-peptides presented by the same HLA molecules.

Other names
HHV-6 pMHCHHV-6 peptide-MHC complexHHV-6 antigen-HLA complexHHV-6 epitope-HLA complex
02

Mechanism of action

Recognition of the peptide-HLA complex by the T-cell receptor (TCR) of therapeutic or endogenous T cells, triggering cytotoxic activity and cytokine release to eliminate infected cells [PubMed: 24109115].

03

Biological functions

Antigen presentationImmune responseT-cell activationViral surveillance
04

Disease associations

InfectionEncephalitisGraft-versus-host diseaseRoseola infantumPneumonitis
05

Safety considerations

Off-target cross-reactivity with self-peptidesCytokine release syndrome (CRS)Graft-versus-host disease (GvHD) in allogeneic settingsImmune evasion by viral downregulation of HLA
06

Interacting drugs

Posoleucel (ALVR105)

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeHHV-6 viral DNA loadPeptide-MHC tetramer-positive T-cell frequencyInterferon-gamma release assay (IGRA)

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