Adenovirus peptide–Human Leukocyte Antigen complex (Ad-pHLA)

Adenovirus peptide–Human Leukocyte Antigen (HLA) complexes are molecular assemblies presented on the surface of cells infected with human adenovirus (HAdV). These complexes consist of short viral peptides, typically 8–11 amino acids in length and often derived from the highly conserved hexon or penton proteins, non-covalently bound within the peptide-binding groove of host HLA class I molecules (Gosset.ai; NIH PMC4966481). Their primary biological function is to serve as the ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, thereby initiating an adaptive immune response to clear the viral infection (ASM.org; Gosset.ai). In immunocompromised individuals, such as hematopoietic stem cell transplant (HSCT) recipients, the absence of a robust T-cell response to these complexes can lead to disseminated and potentially fatal disease (NIH PMC4966481; MDPI Viruses 2023). Therapeutic strategies targeting these complexes include the adoptive transfer of partially HLA-matched, virus-specific T cells (VSTs), such as posoleucel (ALVR105), which recognize these specific viral epitopes to restore immune control (AlloVir; NIH PMC104693637). However, the virus has evolved mechanisms to evade this recognition, most notably through the E3-19K protein, which retains HLA molecules in the endoplasmic reticulum to prevent the surface presentation of the peptide–HLA complex (NIH PMC4966481; ResearchGate). Understanding the structural basis of these complexes is critical for developing next-generation immunotherapies and vaccines that can overcome viral evasion and provide broad protection across different HLA types.

Other names

Adenovirus peptide–HLA complexAdenovirus-derived peptide-MHC complexAdenoviral epitope-MHC I complexAd-pMHCAdenovirus peptide-MHC class I complexAdenovirus peptide-HLA class I complex

Recognition of the viral peptide–HLA complex by the T-cell receptor (TCR) of adoptively transferred or endogenous CD8+ T cells, leading to targeted lysis of the infected cell and the release of antiviral cytokines such as interferon-gamma (IFN-γ) (ASM.org, 2024; NIH PMC104693637).