Peptide-Major Histocompatibility Complex class I (pMHC I) presenting CMV and EBV antigens (pMHC I (CMV/EBV))

Peptide-Major Histocompatibility Complex class I (pMHC I) complexes are essential components of the adaptive immune system, responsible for presenting intracellularly derived peptides to CD8+ cytotoxic T lymphocytes. In the context of Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV), these complexes display viral epitopes—such as those from CMV pp65 or EBV EBNA and LMP proteins—on the surface of infected cells or antigen-presenting cells [2, 16, 23]. These pMHC complexes serve as the specific recognition targets for T-cell receptors (TCRs), which, upon binding, initiate a cascade leading to the destruction of the infected cell [1, 11]. Therapeutically, these complexes are targeted by adoptive cell therapies, including virus-specific T cells (VSTs) like tabelecleucel and posoleucel, as well as experimental TCR-like antibodies [5, 10, 15]. These treatments are particularly critical for immunocompromised patients, such as transplant recipients, who are at high risk for viral reactivation and associated diseases like post-transplant lymphoproliferative disorder (PTLD) [3, 17, 21]. Challenges in targeting these complexes include the high degree of HLA polymorphism, which requires matching therapies to a patient's specific HLA type, and viral immune evasion strategies that downregulate MHC expression to avoid detection [15, 16].

Other names

CMV/EBV pMHC complexesHLA-restricted viral antigensCMV/EBV peptide-HLA complexesViral peptide-MHC class I complexes

Adoptive T-cell therapies (VSTs) or TCR-like antibodies specifically recognize and bind to the viral peptide-MHC complex on the surface of infected or malignant cells, triggering T-cell activation and subsequent target cell lysis via the release of perforin and granzymes.