Cytomegalovirus phosphoprotein 65 (pp65) peptide-HLA class I complex (CMV pp65-pHLA)

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is the most abundant tegument protein of Human Betaherpesvirus 5 (CMV) and a primary target for the host's cell-mediated immune response (UniProt P06725). During viral infection, pp65 is processed into peptides that are presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, such as the immunodominant HLA-A*02:01-restricted peptide NLVPMVATV (PubMed: 10438931). These peptide-HLA (pHLA) complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering the destruction of infected cells (PubMed: 15507644). In immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation, the absence of effective pp65-specific T-cell immunity can lead to life-threatening CMV reactivation (PubMed: 22535238). Therapeutic approaches targeting these complexes include adoptive cell therapies like posoleucel (ALVR105), which consists of multi-virus specific T cells, and experimental TCR-engineered T cells or TCR-like antibodies designed to bypass natural immune deficiencies (ClinicalTrials.gov NCT04354311). These therapies aim to provide or restore targeted viral clearance by exploiting the high specificity of the pp65-pHLA interaction.

Other names

CMV pp65-MHC class I complexUL83 peptide-HLA complexCMV pp65 antigenHLA-A*02:01/NLVPMVATV complexCytomegalovirus UL83 peptide-MHC complex

Recognition of the viral peptide-HLA complex by T-cell receptors (TCRs) or TCR-like molecules, leading to the activation of cytotoxic T lymphocytes and subsequent lysis of CMV-infected cells.