Cytomegalovirus phosphoprotein 65 and immediate-early protein 1 peptide-major histocompatibility complex (CMV pp65/IE1 pMHC)

Cytomegalovirus (CMV) phosphoprotein 65 (pp65) and immediate-early protein 1 (IE1) peptide-major histocompatibility complex (pMHC) molecules are cell-surface structures essential for the immune recognition of CMV-infected cells (Sylwester et al., 2005). The pp65 (UL83) and IE1 (UL123) proteins are the primary immunodominant targets of the host's cellular immune response during both acute and latent phases of infection (UniProt P06725, P13202). These viral proteins are proteolytically processed into short peptides, such as the well-characterized NLVPMVATV epitope, and loaded onto MHC Class I molecules for presentation to CD8+ cytotoxic T lymphocytes (Stern et al., 2019). In immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation, the failure of the endogenous immune system to recognize these complexes can lead to severe CMV disease and organ failure. Therapeutic interventions targeting these pMHC complexes include adoptive cell therapies using virus-specific T cells (VSTs) and the development of TCR-mimetic antibodies designed to trigger the selective destruction of infected cells (ClinicalTrials.gov NCT04354831). These therapies aim to restore protective immunity and control viral replication by leveraging the high specificity of the TCR-pMHC interaction.

Other names

CMV pp65/IE1 peptide-HLA complexUL83/UL123 peptide-MHCCytomegalovirus-specific pMHCHLA-restricted CMV antigen complex

Recognition of specific viral peptide-MHC complexes by the T-cell receptor (TCR) of cytotoxic CD8+ T cells, leading to the release of perforin and granzymes and subsequent apoptosis of the infected cell.