Peptide-Major Histocompatibility Complex presenting Cytomegalovirus (pp65, IE-1), Epstein-Barr Virus (EBNA-1, LMP2), and Adenovirus (Hexon, Penton) epitopes (pMHC-CMV/EBV/AdV)

These peptide-MHC (pMHC) complexes represent the presentation of specific viral antigens on the surface of infected host cells, serving as the primary recognition signal for the cellular immune system (Janeway's Immunobiology, 2017). The target encompasses epitopes derived from six key viral proteins: Cytomegalovirus (CMV) pp65 (UL83) and IE-1 (UL123), Epstein-Barr Virus (EBV) EBNA-1 and LMP2, and Adenovirus (AdV) Hexon and Penton (AlloVir, 2023; UniProt P06725, P03211). These proteins are processed intracellularly and loaded onto Major Histocompatibility Complex (MHC) molecules for recognition by T-cell receptors (TCRs). In immunocompromised patients, such as those post-hematopoietic stem cell transplant, the failure of endogenous T cells to recognize these pMHC complexes leads to severe, often fatal, viral infections (Papadopoulou et al., Science Translational Medicine, 2014). Therapeutic interventions like Posoleucel (ALVR106) utilize allogeneic, multi-virus specific T cells (VSTs) designed to bind these specific pMHC targets and trigger the destruction of infected cells (ClinicalTrials.gov NCT04354805). By targeting multiple viral epitopes simultaneously, these therapies aim to restore broad antiviral immunity and reduce viral loads across several pathogens. The specificity of the TCR-pMHC interaction is critical to minimize off-target effects and the risk of graft-versus-host disease (GvHD) in the allogeneic setting.

Other names

Viral peptide-HLA complexesCMV/EBV/AdV pMHC complexesMulti-virus antigen-MHC complexesPosoleucel target antigensViral-specific T-cell targets

Recognition by T-cell receptors (TCRs) on adoptively transferred virus-specific T cells (VSTs), leading to targeted lysis of infected cells and reduction of viral load.