Viral peptide-Major Histocompatibility Complex (pMHC) on virus-infected host cells (Viral pMHC)

Virus-infected host cells presenting antigens from Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Adenovirus (AdV), Human Herpesvirus 6 (HHV6), and BK Virus (BKV) serve as the primary target for virus-specific T-cell (VST) therapies [1, 2]. These cells process internal viral proteins into short peptide fragments, which are then displayed on the cell surface bound to Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) [3]. This presentation is the critical signal for the adaptive immune system, specifically cytotoxic T lymphocytes, to identify and destroy infected cells [4]. In immunocompromised individuals, such as those undergoing hematopoietic stem cell or solid organ transplantation, the natural T-cell response is often insufficient to control viral reactivation, leading to life-threatening complications like pneumonia, colitis, or encephalitis [1, 3]. Therapeutic strategies like posoleucel utilize ex vivo expanded, donor-derived T cells that are trained to recognize these specific viral pMHC complexes [2, 3]. Upon infusion, these VSTs bind to the target cells, release perforins and granzymes, and induce apoptosis, thereby controlling the infection without the broad toxicity associated with traditional antiviral drugs [4]. [1] Papadopoulou, A., et al. (2013). Science Translational Medicine. [2] AlloVir. Posoleucel (ALVR105). [3] Tzannou, I., et al. (2017). Journal of Clinical Oncology. [4] Pei, X. Y., et al. (2022). Frontiers in Immunology.

Other names

CMV/EBV/AdV/HHV6/BKV peptide-HLA complexesVirus-specific T-cell targetsMulti-virus infected cellsViral antigen-presenting cells

Adoptive transfer of virus-specific T-cells that recognize viral peptides presented by MHC molecules, leading to targeted lysis of infected cells and reduction of viral load [3, 4].