Cytomegalovirus phosphoprotein 65 (pp65) peptide–Major Histocompatibility Complex (MHC) class I complex (CMV pp65-MHC I complex)

The Cytomegalovirus phosphoprotein 65 (pp65) peptide–Major Histocompatibility Complex (MHC) class I complex is a critical immunological target formed when the pp65 protein, encoded by the UL83 gene, is processed and presented on the surface of infected or malignant cells [UniProt: P06725]. As the most abundant tegument protein of Human Cytomegalovirus (HCMV), pp65 is the primary target for the host's cell-mediated immune response, specifically CD8+ cytotoxic T lymphocytes [PubMed: 28923845]. In the context of infectious disease, this complex serves as a marker for CMV-infected cells, particularly in immunocompromised patients such as transplant recipients. Interestingly, pp65 has also been identified as a tumor-associated antigen in several cancers, most notably glioblastoma multiforme, where it is expressed in tumor cells but absent in healthy brain tissue [PubMed: 21540349]. Therapeutic strategies targeting this complex include adoptive T-cell therapies, TCR-engineered T cells (TCR-T), and TCR-like antibodies or bispecific engagers [AlloVir]. These therapies aim to leverage the high specificity of the TCR-pMHC interaction to selectively eliminate CMV-positive cells while sparing healthy tissue.

Other names

CMV pp65-HLA-A*02:01 complexpp65-MHC complexCMV antigen-MHC class I complexUL83 peptide-MHC complexNLVPMVATV-HLA-A*02:01 complex

Recognition by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the activation of the T cell and subsequent lysis of the target cell presenting the CMV pp65 peptide [PubMed: 28923845].