Viral peptide–Major Histocompatibility Complex (pMHC) complexes (EBV, CMV, Adenovirus) (Viral pMHC (EBV/CMV/AdV))

Viral peptide–Major Histocompatibility Complex (pMHC) complexes are the fundamental units of recognition for the adaptive immune system, specifically for T-cells. These complexes are formed when intracellular viral proteins from Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), or Adenovirus are processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules [Murphy K, Weaver C. Janeway's Immunobiology. 9th ed.]. In healthy individuals, cytotoxic T-lymphocytes (CTLs) recognize these pMHC complexes via their T-cell receptors (TCRs), triggering the destruction of the infected cell. However, in immunocompromised patients, such as those receiving hematopoietic stem cell transplants (HSCT) or solid organ transplants (SOT), the absence of a robust T-cell response allows these viruses to reactivate, leading to severe conditions like post-transplant lymphoproliferative disorder (PTLD) or systemic infections [Prockop S, et al. J Clin Oncol. 2020]. Therapeutic interventions, such as adoptive T-cell therapies (e.g., Tabelecleucel and Posoleucel), utilize donor-derived or engineered T-cells that specifically target these viral pMHC complexes to restore immune control [EMA. Ebvallo Summary of Product Characteristics. 2022]. These therapies are designed to be HLA-restricted, meaning they must match the specific MHC alleles of the patient to effectively recognize the viral targets and avoid off-target effects [Tzannou I, et al. J Clin Oncol. 2017]. By binding to these complexes, the therapeutic T-cells induce targeted apoptosis of the infected cells, effectively reducing viral load and treating associated pathologies [AlloVir. Posoleucel (ALVR105) Overview. 2023].

Other names

Viral pMHC complexesHLA-peptide complexesVirus-specific MHC-peptide complexesEBV/CMV/AdV antigen-MHC complexesViral pMHCs

Recognition of viral peptide-MHC complexes by T-cell receptors (TCRs) on adoptive T-cell therapies, leading to targeted cytotoxicity of infected cells [Tzannou I, et al. J Clin Oncol. 2017].