Human herpesvirus 6 peptide–HLA class I complex (HHV-6 peptide–HLA-I) (HHV-6 peptide–HLA-I)

Human herpesvirus 6 (HHV-6) peptide–HLA class I complexes are molecular assemblies presented on the surface of cells infected with HHV-6A or HHV-6B. These complexes are formed when viral proteins, such as U14, U54, or U90, are processed into short peptides and loaded onto Human Leukocyte Antigen (HLA) class I molecules (PubMed: 26179483). Once displayed on the cell surface, they act as the specific ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the virus (PubMed: 30305453). In clinical contexts, HHV-6 reactivation is a major cause of morbidity in hematopoietic stem cell and solid organ transplant recipients, contributing to encephalitis and pneumonitis (NIH: PMC4717285). These complexes are the primary targets for investigational virus-specific T-cell (VST) therapies, such as posoleucel, which are designed to provide passive immunity to immunocompromised patients (AlloVir, 2023). Successful targeting depends on the presence of specific HLA alleles, making HLA typing a critical component of patient selection. Potential challenges include the virus's ability to downregulate HLA expression to evade immune detection and the risk of T-cell cross-reactivity with host tissues.

Other names

HHV-6 pMHC complexHHV-6 peptide-MHC class I complexHuman herpesvirus 6 antigen-HLA complexHHV-6 p/HLA-I

T-cell receptor (TCR) binding and subsequent cytotoxic T-lymphocyte (CTL) mediated lysis of infected cells.