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

The Cytomegalovirus (CMV) phosphoprotein 65 (pp65) peptide–Major Histocompatibility Complex (MHC) class I complex is a molecular assembly presented on the surface of cells infected with Human Cytomegalovirus (HCMV) (UniProt P06725). It consists of a peptide fragment derived from the pp65 tegument protein, encoded by the UL83 gene, bound within the groove of an MHC class I molecule (Wills et al., 1996, PubMed: 8642361). This complex serves as a critical signal for the immune system, specifically identifying infected cells for destruction by CD8+ cytotoxic T lymphocytes (Diamond et al., 1999, PubMed: 10438932). The most well-characterized version of this target involves the NLVPMVATV peptide presented by the HLA-A*02:01 allele. In immunocompromised individuals, such as transplant recipients, the failure of the immune system to recognize these complexes leads to viral reactivation and severe disease. Consequently, this complex is a major focus for immunotherapy, including the development of adoptive T-cell transfers and TCR-engineered T cells (Schub et al., 2009, PubMed: 28246207). These therapies aim to restore or enhance the patient's ability to target and eliminate CMV-infected cells by binding specifically to the pp65-MHC assembly. Research also explores TCR-like antibodies and bispecific engagers that can redirect non-specific T cells to these viral targets (ClinicalTrials.gov: NCT02138409).

Other names

CMV pp65-HLA complexHLA-A*02:01/NLVPMVATV complexUL83 peptide-MHC complexCMV pp65-MHC I

Recognition by specific T-cell receptors (TCRs) on CD8+ T cells, triggering the release of cytotoxic granules and apoptosis of the infected cell.