Cytomegalovirus phosphoprotein 65 (pp65) and immediate-early protein 1 (IE-1) peptides presented on human leukocyte antigen (HLA) class I (CMV pp65/IE-1 HLA-I complex)

Cytomegalovirus (CMV) phosphoprotein 65 (pp65, encoded by UL83) and immediate-early protein 1 (IE-1, encoded by UL123) are dominant antigens presented by Human Leukocyte Antigen (HLA) class I molecules on the surface of CMV-infected cells (PMID: 15939751). pp65 is a major tegument protein that is highly immunogenic, while IE-1 is a critical regulatory protein expressed immediately upon viral entry or reactivation (PMID: 22438551). These peptide-HLA complexes serve as the primary targets for CD8+ cytotoxic T-lymphocytes (CTLs), which are essential for controlling CMV infection and preventing progression to symptomatic disease in healthy individuals (UniProt: P06725, P13202). In immunocompromised patients, such as hematopoietic stem cell or solid organ transplant recipients, the absence of a robust T-cell response against these targets leads to high morbidity and mortality (PMID: 28202434). Therapeutic approaches targeting these complexes include the adoptive transfer of donor-derived or ackslash"off-the-shelfackslash" virus-specific T cells (VSTs), such as Posoleucel, and the development of vaccines like Triplex that aim to elicit endogenous T-cell responses (ClinicalTrials.gov: NCT04354805). These therapies leverage the specificity of the T-cell receptor (TCR) for the pp65/IE-1 peptides in the context of specific HLA alleles to selectively eliminate infected cells.

Other names

CMV pp65/IE-1 MHC-I complexUL83/UL123 HLA-I complexCMV-specific peptide-MHC complexespp65/IE-1 epitopes

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) activation leading to lysis of infected cells.