Adenovirus, Cytomegalovirus, and Epstein-Barr Virus peptide-HLA complexes (AdV/CMV/EBV-pMHC)

This target consists of viral peptides derived from Adenovirus (AdV), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV) presented on the cell surface by Human Leukocyte Antigen (HLA) Class I and II molecules. These peptide-HLA (pMHC) complexes serve as the primary recognition signal for the cellular immune system, specifically for CD8+ and CD4+ T-lymphocytes (Papadopoulou et al., 2014). In immunocompromised settings, such as following hematopoietic stem cell or solid organ transplantation, the failure of the host immune system to recognize these complexes leads to viral reactivation and significant morbidity (Prockop et al., 2020). Therapeutic interventions like Tabelecleucel and Posoleucel utilize allogeneic, off-the-shelf virus-specific T-cells (VSTs) that are pre-screened to match the patient's HLA alleles and recognize these specific viral antigens (AlloVir, 2023). Upon recognition of the pMHC complex, the VSTs proliferate and release cytotoxic granules, such as granzyme and perforin, to selectively eliminate the virus-infected cells. This targeted approach aims to restore viral immunity without the broad myelosuppression or nephrotoxicity associated with traditional antiviral drugs like ganciclovir or cidofovir. The efficacy of these therapies is highly dependent on the correct presentation of these peptides and the matching of HLA alleles between the donor-derived T-cells and the recipient's infected cells.

Other names

AdV/CMV/EBV peptide-MHC complexesViral peptide-HLA complexesVirus-specific T-cell targetsMultivirus-specific antigen-presenting complexes

Recognition of viral peptide-HLA complexes by the T-cell receptor (TCR) of adoptively transferred virus-specific T-cells (VSTs), leading to targeted lysis of infected cells.