Human leukocyte antigen-restricted adenovirus hexon-derived peptide–major histocompatibility complex (HLA-AdV hexon pMHC)

Human leukocyte antigen (HLA)-restricted adenovirus hexon-derived peptide–major histocompatibility complex (pMHC) refers to the molecular assembly of a specific adenovirus hexon protein fragment presented by HLA molecules on the surface of infected cells (Feuchtinger et al., 2004, doi:10.1111/j.1365-2141.2004.05009.x). The hexon protein is the most abundant structural protein of the adenovirus capsid and contains highly conserved regions that serve as dominant targets for T-cell mediated immunity (Leen et al., 2006, doi:10.1182/blood-2006-05-024760). These complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells and CD4+ helper T cells, which is a critical step in the natural clearance of adenovirus infections (Aiello et al., 2017, doi:10.1128/JVI.00444-17). In immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation, the failure of this immune recognition can lead to life-threatening systemic infection (Papadopoulou et al., 2014, doi:10.1126/scitranslmed.3008825). Consequently, these pMHC complexes are the primary targets for adoptive immunotherapies, including viral-specific T cells (VSTs) and TCR-engineered T cells (Gerdemann et al., 2012, doi:10.1038/mt.2012.153). Therapeutic strategies like Posoleucel utilize the specificity of T cells for these hexon-derived epitopes to restore antiviral immunity in patients (AlloVir, 2023). The identification of specific immunodominant peptides, such as those restricted by HLA-A*01 or HLA-A*02, allows for the development of off-the-shelf T-cell products that can be matched to a patient's HLA type.

Other names

Adenovirus hexon peptide-HLA complexAdV hexon pMHCHLA-restricted adenovirus epitopeAdenovirus hexon antigen-MHC complexHexon-derived pMHC

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD4+ or CD8+ T cells, triggering cytotoxic activity and cytokine release to eliminate adenovirus-infected cells.