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

Cytomegalovirus phosphoprotein 65 (pp65), also known as UL83, is a 65 kDa tegument protein that constitutes a significant portion of the Human Cytomegalovirus (HCMV) virion (UniProt: P06725). It is the primary target of the host's cellular immune response, particularly CD8+ cytotoxic T lymphocytes (CTLs). During infection, pp65 is processed by the proteasome into short peptides, such as the immunodominant NLVPMVATV sequence, which are then loaded onto Human Leukocyte Antigen (HLA) class I molecules for presentation on the cell surface (PubMed: 15141013). This peptide-MHC complex serves as a critical molecular signature for the immune system to identify and destroy infected cells. In clinical practice, this complex is targeted by adoptive T-cell therapies and vaccines to prevent or treat CMV reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (PubMed: 25609777). The specificity of the interaction between the T-cell receptor and the pp65/HLA complex is vital for therapeutic efficacy and the avoidance of off-target effects.

Other names

HCMV pp65 peptide-MHC complexUL83 peptide-HLA complexCMV pp65/HLA-A*02:01CMV pp65 antigen-HLA complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the release of perforin and granzymes and subsequent apoptosis of the CMV-infected cell (PubMed: 15141013).