Cytomegalovirus peptide–Major Histocompatibility Complex class I complex (CMV peptide–MHC I)

Cytomegalovirus (CMV) peptide–Major Histocompatibility Complex (MHC) class I complexes are the primary molecular targets for CD8+ cytotoxic T-lymphocyte (CTL) recognition of CMV-infected cells (Reddehase, 2002, PMID: 12117470). These complexes consist of viral peptides, predominantly derived from the pp65 (UL83) and IE1 (UL123) proteins, presented on the cell surface in association with MHC class I molecules (Arvin et al., 2007). Their biological function is to signal the presence of intracellular viral replication, triggering T-cell activation and subsequent lysis of the infected cell. In therapeutic contexts, these complexes are targeted by adoptive T-cell therapies and TCR-engineered cells to treat CMV infections in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (ClinicalTrials.gov, NCT04354831). A major challenge in targeting these complexes is the virus's sophisticated immune evasion strategy, which involves the expression of immunoevasins like US2 and US11 that degrade MHC class I molecules to prevent surface presentation (Hansen et al., 2010, PMID: 20413920). Consequently, the density of these complexes on the cell surface is a critical determinant of immune clearance and therapeutic efficacy. Monitoring the presence of these complexes via HLA-restricted multimers is a standard technique in assessing CMV-specific immunity.

Other names

CMV pMHCHCMV peptide-HLA complexCMV antigen-MHC complexpp65 peptide-MHC complexIE1 peptide-MHC complexCMV-specific pMHC

Recognition by specific T-cell receptors (TCRs) on CD8+ T cells, leading to the formation of an immunological synapse and the release of cytotoxic granules (perforin/granzyme) to induce apoptosis in the infected cell.