Cytomegalovirus phosphoprotein 65 epitopes presented on Human Leukocyte Antigen A*11:01 (CMV pp65/HLA-A*11:01)

The CMV pp65 epitopes presented on HLA-A*11:01 represent a specific peptide-major histocompatibility complex (pMHC) target used by the immune system to identify and eliminate cells infected with Human Cytomegalovirus (CMV). Phosphoprotein 65 (pp65), encoded by the UL83 gene, is the most abundant tegument protein of CMV and serves as a dominant antigen for CD8+ cytotoxic T-cell responses (PMID: 7525835). In individuals carrying the HLA-A*11:01 allele—which is highly prevalent in East and Southeast Asian populations—specific pp65-derived peptides, such as ATDQVAKV, are processed and displayed on the cell surface (PMID: 10933588). This complex is a critical target for adoptive cellular therapies, including virus-specific T-cells (VSTs) and TCR-engineered T-cells, designed to treat or prevent CMV disease in immunocompromised patients, such as hematopoietic stem cell transplant recipients (PMID: 25605930). By specifically recognizing this pMHC, therapeutic T-cells can selectively induce apoptosis in infected cells, thereby controlling viral replication. Therapeutic interventions often involve the infusion of donor-derived or autologous T-cells that have been expanded or engineered to recognize these specific epitopes. Challenges in targeting this complex include viral mechanisms that downregulate HLA expression to evade immune detection. Additionally, there is a potential for off-target reactivity if the therapeutic TCR recognizes similar self-peptides, necessitating rigorous safety screening. The HLA-A*11:01 restriction makes these therapies particularly relevant for specific ethnic populations where this allele is common. Monitoring of CMV DNA viral load and pp65-specific T-cell counts serves as a primary method for assessing treatment efficacy.

Other names

CMV pp65/HLA-A*11:01 complexHLA-A*11:01-restricted CMV pp65 epitopesUL83 epitopes on HLA-A*11:01CMV pp65 peptide-HLA-A*11:01

Recognition of the specific pp65 peptide-HLA-A*11:01 complex by the T-cell receptor (TCR) of CD8+ cytotoxic T-lymphocytes, triggering the release of perforin and granzymes to induce apoptosis in CMV-infected cells.