Human leukocyte antigen A*24:02–Cytomegalovirus 65 kDa phosphoprotein peptide complex (HLA-A*24:02–CMV pp65 complex)

The Human leukocyte antigen A*24:02–Cytomegalovirus 65 kDa phosphoprotein peptide complex is a molecular assembly consisting of the MHC Class I allele HLA-A*24:02 and an immunodominant peptide derived from the Cytomegalovirus (CMV) pp65 protein, such as QYDPVAALF or VYALPLKML (Akiyama et al., 2002; Miltenyi Biotec). This complex is presented on the surface of CMV-infected cells and is essential for the recognition and elimination of the virus by CD8+ cytotoxic T lymphocytes (Akiyama et al., 2004). In clinical settings, particularly following hematopoietic stem cell or solid organ transplantation, the reactivation of CMV poses a significant risk to immunocompromised patients (Zhang et al., 2022). The complex serves as a primary target for novel immunotherapies, including T-cell receptor (TCR)-engineered T cells and peptide-based vaccines designed to restore or enhance viral immunity (Zhang et al., 2022; JPT Peptide Technologies). TCR-T therapies utilize engineered T cells that express a specific TCR capable of binding this MHC-peptide complex, leading to the targeted destruction of infected cells (Zhang et al., 2022). Furthermore, MHC tetramers specific to this complex are widely used as diagnostic tools to monitor the reconstitution of CMV-specific T-cell immunity and to predict the risk of clinical CMV disease (Akiyama et al., 2004; MBL International). Therapeutic challenges include the potential for cytokine release syndrome and the need for precise patient selection based on HLA typing (Zhang et al., 2022).

Other names

HLA-A24-CMV pp65 complexHLA-A*24:02-QYDPVAALF complexHLA-A*24:02-VYALPLKML complexCMV pp65-HLA-A*24:02 complexMHC-peptide complex (HLA-A*24:02/pp65)

The complex acts as a ligand for T-cell receptors (TCRs). Therapeutic strategies involve the use of TCR-engineered T cells (TCR-T) that specifically recognize this complex on the surface of CMV-infected cells, triggering T-cell activation and subsequent lysis of the target cell. Alternatively, peptide vaccines utilize synthetic epitopes from the complex to stimulate an endogenous cytotoxic T lymphocyte (CTL) response.