Cytomegalovirus immediate-early 1 peptide–major histocompatibility complex class I complex (CMV IE1–MHC I complex)

The Cytomegalovirus (CMV) immediate-early 1 (IE1) peptide–major histocompatibility complex (MHC) class I complex is a molecular assembly presented on the surface of cells infected with human cytomegalovirus (HCMV). IE1, encoded by the UL123 gene, is one of the first viral proteins synthesized upon infection or reactivation and is essential for viral replication and the subversion of host defenses (Khan et al., 2002, PMID: 12357477). The complex is formed when IE1-derived peptides, such as the immunodominant VLEETSVML peptide, are processed and loaded onto MHC class I molecules (e.g., HLA-A*02:01) for presentation to the immune system (Wills et al., 1996, PMID: 8934465). This peptide-MHC (pMHC) complex acts as a specific ligand for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which trigger the apoptosis of the infected cell upon recognition. In therapeutic development, this complex is a primary target for adoptive T-cell therapies and TCR-engineered T cells (TCR-T) aimed at restoring CMV-specific immunity in immunocompromised individuals, such as hematopoietic stem cell or solid organ transplant recipients (Schub et al., 2009, PMID: 19710464). Because IE1 is expressed very early in the viral cycle, targeting this complex allows the immune system to intercept and eliminate infected cells before the production of infectious progeny.

Other names

HCMV IE1-HLA complexIE1 peptide-MHC class I complexCMV IE1-pMHCHLA-A*02:01-restricted IE1 peptide complexUL123 peptide-MHC complex

Recognition by specific T-cell receptors (TCRs) or TCR-like molecules leading to the targeted lysis of infected cells by cytotoxic T lymphocytes (CTLs) or through antibody-dependent cellular cytotoxicity (ADCC).