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

The Cytomegalovirus (CMV) phosphoprotein 65 (pp65) peptide-Major Histocompatibility Complex (MHC) class I complex is a primary immunological target for the control of CMV infection. CMV pp65, encoded by the UL83 gene, is the most immunodominant internal matrix protein of the virus and is processed into short peptides, such as the widely studied NLVPMVATV epitope, which are then presented on the cell surface by MHC class I molecules (typically HLA-A*02:01) [1][2]. These complexes are essential for the recognition and elimination of infected cells by CD8+ cytotoxic T lymphocytes (CTLs). In clinical settings, this complex is a major focus for adoptive immunotherapy, particularly in hematopoietic stem cell and solid organ transplant recipients who face life-threatening CMV reactivation due to immunosuppression [3]. Furthermore, the presence of CMV pp65 antigens in certain malignancies, such as glioblastoma multiforme, has led to the development of TCR-engineered T-cell therapies and vaccines targeting these specific peptide-MHC complexes to induce anti-tumor immunity [4]. Therapeutic strategies include the use of virus-specific T-cells (VSTs) and bispecific molecules designed to bridge the complex with effector T-cells to ensure targeted cell lysis [5]. Sources: [1] UniProt (P06725 - UL83_HCMVA) [2] Stern et al. (2019) "CMV-specific T-cell therapy," Frontiers in Immunology [3] ClinicalTrials.gov (NCT04354311 for Posoleucel) [4] Cobbs et al. (2002) "Human cytomegalovirus infection and expression in human malignant glioma," Cancer Research [5] Atara Biotherapeutics and AlloVir pipeline documentation.

Other names

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

Recognition by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering the release of perforins and granzymes to induce apoptosis in the target cell presenting the viral peptide.