Adenovirus peptide-Major Histocompatibility Complex (Adv-pMHC)

Peptide–MHC complexes presenting adenovirus antigens are critical molecular assemblies on the surface of infected host cells that signal the presence of a viral pathogen to the immune system [PMID: 28923814]. These complexes consist of a viral peptide fragment, typically derived from adenoviral proteins like hexon or penton base, bound within the groove of a Major Histocompatibility Complex (MHC) molecule, most commonly MHC Class I [UniProt: P03277]. The primary biological function of these complexes is to serve as a ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering an immune response to eliminate the infected cell [PMID: 31209119]. In the context of disease, adenovirus can cause severe, life-threatening infections in immunocompromised individuals, such as hematopoietic stem cell transplant recipients [NIH: StatPearls - Adenovirus]. Therapeutic strategies targeting these complexes include the infusion of donor-derived virus-specific T cells (VSTs), such as Posoleucel, or the development of TCR-like antibodies and bispecific molecules that mimic TCR specificity [Allovir, 2023]. These therapies aim to restore or augment the host's ability to clear the virus by specifically recognizing and lysing cells displaying the adenoviral pMHC. Challenges include the high polymorphism of HLA molecules and the ability of some adenoviruses to downregulate MHC expression via the E3-19K protein to evade detection [PMID: 15608363].

Other names

Adenoviral peptide-HLA complexAdenovirus antigen-MHC complexMHC-presented adenovirus peptidesAdenovirus pMHC

T-cell receptor-mediated recognition and subsequent cytotoxic lysis of infected cells