Cytomegalovirus phosphoprotein 65-derived peptide epitopes presented by Human Leukocyte Antigen class I (CMV pp65/HLA-I)

Cytomegalovirus (CMV) phosphoprotein 65 (pp65), encoded by the UL83 gene, is the primary tegument protein and a dominant target of the host immune response during CMV infection (UniProt: P06725). Peptide epitopes derived from pp65 are processed intracellularly and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, where they are recognized by CD8+ cytotoxic T lymphocytes (PubMed: 15958661). This recognition is crucial for controlling CMV latency and reactivation, particularly in immunocompromised individuals such as hematopoietic stem cell or solid organ transplant recipients (PubMed: 28232599). In therapeutic contexts, these peptide-MHC complexes serve as targets for adoptive T-cell therapies, TCR-engineered T cells, and peptide-based vaccines designed to restore or enhance CMV-specific immunity (ClinicalTrials.gov: NCT02396134). The most well-characterized epitope is the HLA-A*02:01-restricted NLVPMVATV peptide, which is frequently used in diagnostic assays and therapeutic development. Targeting this complex allows for the selective elimination of CMV-infected cells while sparing healthy, non-infected tissue. Current clinical strategies include the use of multi-virus specific T cells and recombinant vaccines to boost the T-cell repertoire against these specific epitopes (PubMed: 30154116).

Other names

CMV pp65 peptide-MHC complexUL83-derived HLA-I epitopespp65-HLA complexNLVPMVATV/HLA-A*02:01Cytomegalovirus UL83 peptide-HLA class I complex

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) on CD8+ T cells, leading to the activation of cytotoxic pathways (perforin/granzyme) and the secretion of pro-inflammatory cytokines like IFN-gamma to eliminate CMV-infected cells.