Cytomegalovirus phosphoprotein 65 and immediate-early protein 1 peptide-MHC complexes (CMV pp65/IE1 pMHC)

Cytomegalovirus (CMV) pp65 and IE1 peptide-MHC complexes are the primary molecular targets for the cellular immune system to identify and eliminate CMV-infected cells. The pp65 protein (UL83) is a major structural component of the viral tegument, while IE1 (UL123) is an immediate-early protein essential for viral replication and immune evasion (UniProt: P06725, P13202). These proteins are processed by the host cell's proteasome into peptides that are then loaded onto Major Histocompatibility Complex (MHC) Class I molecules for presentation on the cell surface (PubMed: 25609776). Recognition of these specific peptide-MHC (pMHC) complexes by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes triggers the release of perforin and granzymes, leading to the apoptosis of the infected cell. In the context of therapeutic development, these complexes are the focus of adoptive T-cell therapies and TCR-engineered cells designed to restore CMV-specific immunity in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (PubMed: 17435050). Investigational therapies like posoleucel (ALVR105) leverage this mechanism by providing donor-derived T cells that specifically recognize these viral antigens to control infection and prevent CMV-related diseases.

Other names

CMV-infected cellspp65-HLA complexIE1-HLA complexUL83/UL123 peptide-MHCCMV antigen-MHC complex

T-cell receptor (TCR) mediated recognition of viral peptides presented by MHC molecules, leading to cytotoxic T-lymphocyte (CTL) activation and lysis of the infected cell.