Adenovirus hexon protein-derived peptide–Major Histocompatibility Complex (HAdV-hexon-pMHC)

Adenovirus hexon-derived peptide–MHC complexes are antigenic structures presented on the surface of cells infected with human adenovirus (HAdV) (UniProt P04133). The hexon protein is the most abundant capsid protein and contains highly conserved, immunodominant epitopes that are processed and loaded onto Major Histocompatibility Complex (MHC) molecules (Blood 2004;104:2432-2440). These complexes are essential for the recognition and elimination of infected cells by the host's cellular immune system, primarily through CD8+ cytotoxic T lymphocytes (CTLs) and CD4+ helper T cells (Frontiers in Immunology 2021). In immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (HSCT), the failure of this immune recognition can lead to disseminated and potentially fatal adenovirus infections (NIH.gov). Consequently, these pMHC complexes serve as critical targets for adoptive immunotherapies, including the infusion of donor-derived virus-specific T cells (VSTs) or T cells engineered with specific T-cell receptors (TCR-T) (Molecular Immunology 2013). Therapeutic development focuses on identifying epitopes like LTDLGQNLLY (restricted by HLA-A*01:01) or TYFSLNNKF (restricted by HLA-A*24:02) that are conserved across multiple adenovirus serotypes to provide broad clinical utility (PubMed 23911395). Drugs like posoleucel (ALVR106) utilize T cells that recognize these complexes to restore immunity in vulnerable patients (AlloVir). The interaction between the therapeutic TCR and the pMHC complex triggers the release of cytotoxic granules, effectively clearing the viral reservoir (Blood 2004;104:2432-2440).

Other names

Adenovirus hexon pMHCHAdV hexon-MHC complexAdenovirus hexon epitope-MHC complexHexon peptide-HLA complexAdenovirus hexon-derived peptide–MHC complexes on infected cells

T-cell receptor (TCR) recognition of the peptide-MHC complex leads to T-cell activation and subsequent lysis of the infected cell via perforin and granzyme release (Blood 2004;104:2432-2440).