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

The Cytomegalovirus phosphoprotein 65 (pp65) peptide–HLA class I complex is a critical immunological target found on the surface of cells infected with Human Cytomegalovirus (HCMV). The pp65 protein, encoded by the UL83 gene, is the most abundant tegument protein of the virus and serves as a dominant antigen for the host's cellular immune response (UniProt P06725). During infection, pp65 is processed by the proteasome into short peptides, such as the immunodominant NLVPMVATV sequence, which are then loaded onto HLA class I molecules (most commonly HLA-A*02:01) and transported to the cell surface (PubMed: 10438932). This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering the release of perforins and granzymes to eliminate the infected cell (PubMed: 25533034). In therapeutic contexts, this complex is targeted by adoptive T-cell therapies and engineered TCR-T cells to restore or enhance viral clearance in immunocompromised patients, such as hematopoietic stem cell or solid organ transplant recipients (PubMed: 31534003). Additionally, TCR-like antibodies are being developed to target this pMHC complex directly, providing a potential alternative to cell-based therapies (PubMed: 28257018).

Other names

CMV pp65-MHC complexHLA-A*02:01-restricted CMV pp65 peptideUL83 peptide-HLA complexpp65(495-503) peptide-HLA-A*02:01 complexNLVPMVATV-HLA-A*02:01 complex

Recognition by T-cell receptors (TCRs) or TCR-like molecules leading to the targeted lysis of CMV-infected cells.