Cytomegalovirus pp65-derived peptide–HLA class I complex (CMV pp65-pHLA complex)

The Cytomegalovirus (CMV) pp65-derived peptide–HLA class I complex is a molecular assembly consisting of a fragment of the viral phosphoprotein 65 (pp65) bound to a Human Leukocyte Antigen (HLA) class I molecule [1]. The pp65 protein, encoded by the UL83 gene, is the primary immunodominant target for the host's cellular immune response during CMV infection [2]. A specific nonamer peptide, NLVPMVATV, is frequently presented by the HLA-A*02:01 allele and serves as a major recognition site for CD8+ cytotoxic T lymphocytes (CTLs) [3]. This complex is crucial for the immune system to identify and eliminate CMV-infected cells, particularly in the context of viral reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation [4]. Therapeutic interventions targeting this complex include adoptive T-cell therapies, such as CMV-specific T cells (VSTs) and TCR-engineered T cells, which aim to restore or enhance the patient's ability to control the virus [5]. These therapies work by specifically binding to the peptide-MHC complex, triggering a targeted cytotoxic response against infected cells while sparing healthy tissue [6]. Sources: [1] UniProt Consortium. UL83 - Protein pp65. UniProtKB - P06725. [2] Wills, M. R., et al. (1996). The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65. Journal of Virology. [3] Diamond, D. J., et al. (1997). Development of a candidate HLA-A*0201-restricted peptide-based vaccine against human cytomegalovirus. Blood. [4] Boeckh, M., & Geballe, A. P. (2011). Cytomegalovirus: pathogen, paradigm, and puzzle. Journal of Clinical Investigation. [5] Papadopoulou, A., et al. (2013). Activity of broad-spectrum T cells as treatment for adeno-, EBV-, CMV-, BKV-, and HHV6-infections after HSCT. Science Translational Medicine. [6] ClinicalTrials.gov. Safety and Efficacy of Posoleucel (ALVR106). NCT04350034.

Other names

CMV pp65-MHC complexUL83 peptide-HLA complexNLVPMVATV-HLA-A*02:01 complexCMV phosphoprotein 65-peptide-MHCCMV-pMHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and lysis of CMV-infected cells.