Cytomegalovirus pp65 peptide-Major Histocompatibility Complex (CMV pp65-MHC)

The Cytomegalovirus (CMV) pp65 peptide-Major Histocompatibility Complex (MHC) is a critical immunological target consisting of an 8-11 amino acid fragment of the pp65 (UL83) protein bound to an MHC Class I molecule, most commonly HLA-A*02:01. As the most abundant tegument protein of CMV, pp65 is the primary target for the host's cellular immune response, particularly CD8+ cytotoxic T lymphocytes (UniProt P06725; PubMed: 15905523). In immunocompromised individuals, such as hematopoietic stem cell or solid organ transplant recipients, the failure of the immune system to recognize this complex leads to CMV reactivation and severe clinical disease (PubMed: 28235143). Therapeutic strategies targeting this complex include adoptive T-cell therapies, TCR-engineered T-cells, and peptide-based vaccines designed to restore or enhance the immune system's ability to eliminate CMV-infected cells (ClinicalTrials.gov: NCT02390141). Additionally, because pp65 has been detected in certain malignancies like glioblastoma, this pMHC complex is being explored as a tumor-associated viral antigen for cancer immunotherapy (PubMed: 25762132). Drugs interacting with this target typically function by mimicking or enhancing the natural TCR-MHC interaction to trigger apoptosis in cells presenting the viral epitope.

Other names

CMV pp65-HLA complexUL83 peptide-MHCpp65-MHC Class I complexHLA-A*02:01-NLVPMVATV complexCytomegalovirus 65 kDa phosphoprotein-MHC

Recognition by T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes or TCR-like antibodies, leading to the targeted lysis of infected or malignant cells through the release of perforins and granzymes.