Human leukocyte antigen class I-restricted cytomegalovirus pp65 peptide-MHC complex (CMV pp65-pMHC)

The Human leukocyte antigen (HLA) class I-restricted cytomegalovirus (CMV) pp65 peptide-MHC complex is a molecular assembly presented on the surface of cells infected with Human Cytomegalovirus (HCMV). It consists of a processed peptide fragment from the 65 kDa phosphoprotein (pp65, also known as UL83), which is the most abundant tegument protein of the virus, bound to an HLA class I molecule (UniProt P06725; PubMed 7525834). This complex serves as a primary target for the host's cellular immune system, specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs). Recognition of this complex is essential for the immune-mediated control of CMV, a virus that remains latent in the majority of the population but can cause severe, life-threatening disease in immunocompromised individuals, such as transplant recipients (PubMed 31533957). In the context of drug development, this complex is targeted by various immunotherapies, including adoptive transfer of CMV-specific T cells and engineered TCR-T cell therapies. These treatments aim to restore or enhance the patient's ability to eliminate CMV-infected cells by providing T cells that specifically bind to the pp65-derived peptides (e.g., the NLVPMVATV peptide restricted by HLA-A*02:01) presented by the MHC (PubMed 25609774). While highly effective, targeting these complexes requires precise HLA matching and carries risks such as cytokine release syndrome or potential cross-reactivity with self-peptides that might mimic the viral epitope.

Other names

CMV pp65-HLA complexUL83 peptide-MHC complexHLA-A*02:01/NLVPMVATV complexCMV pp65(495-503) peptide-MHCCytomegalovirus pp65-derived peptide-MHC class I complex

Recognition by antigen-specific T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) activation and lysis of infected cells.