Cytomegalovirus phosphoprotein 65-derived peptide-HLA complex (CMV pp65-HLA)

The Cytomegalovirus phosphoprotein 65 (pp65)-derived peptide-HLA complex is a molecular assembly consisting of an 8-11 amino acid peptide derived from the CMV UL83 protein (pp65) bound within the groove of a Human Leukocyte Antigen (HLA) class I or II molecule [1, 2]. As the most abundant tegument protein of CMV, pp65 is the primary target for the host's cell-mediated immune response, specifically for CD8+ cytotoxic T lymphocytes [2]. This complex is expressed on the surface of CMV-infected cells and has also been identified as a tumor-associated viral antigen in certain malignancies, most notably glioblastoma multiforme [4]. In clinical practice, this complex is targeted by virus-specific T-cell (VST) therapies and TCR-engineered T-cells to restore immunity in immunocompromised transplant recipients or to direct an immune attack against pp65-expressing tumor cells [3, 5]. Therapeutic interventions often focus on specific immunodominant epitopes, such as the NLVPMVATV peptide presented by HLA-A*02:01 [2]. The recognition of this complex by the immune system is a cornerstone of CMV management in hematopoietic stem cell and solid organ transplantation. Sources: [1] UniProt P06725; [2] Wills et al., J Virol 1996; [3] Papadopoulou et al., Sci Transl Med 2014; [4] Schuessler et al., Cancer Res 2014; [5] Smith et al., Expert Opin Biol Ther 2017.

Other names

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

The mechanism of action involves the specific recognition of the peptide-HLA complex by the T-cell receptor (TCR) of cytotoxic T lymphocytes (CTLs) or engineered T-cells, leading to the release of perforins and granzymes that induce apoptosis in the target cell [2, 5].