Cytomegalovirus phosphoprotein 65 (pp65) peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) (CMV pp65/HLA-A*02:01)

The CMV pp65 peptide presented by HLA-A*02:01 is a critical molecular target for the immune system's control of Human Cytomegalovirus (CMV). This target consists of the immunodominant 9-amino acid peptide NLVPMVATV, derived from the viral tegument phosphoprotein 65 (pp65, also known as UL83), which is processed and displayed on the cell surface by the MHC class I molecule HLA-A*02:01 [PubMed: 15905523, UniProt: P06725]. Recognition of this specific peptide-MHC (pMHC) complex by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs) is the primary mechanism for the elimination of CMV-infected cells in healthy individuals [IEDB: 45139]. In patients with compromised immune systems, such as those undergoing hematopoietic stem cell or solid organ transplantation, the failure to mount an effective T-cell response against this target can lead to severe clinical disease, including pneumonia, hepatitis, and retinitis. Therapeutic strategies targeting the CMV pp65/HLA-A*02:01 complex include the adoptive transfer of donor-derived or off-the-shelf CMV-specific T cells (e.g., posoleucel) and the administration of peptide or viral-vector vaccines (e.g., PepVax, Triplex) designed to stimulate endogenous CTL responses [ClinicalTrials.gov: NCT02396134, NCT02464657]. Additionally, novel TCR-engineered T-cell therapies (TCR-T) are being developed to provide high-affinity recognition of this complex for patients lacking natural immunity. Monitoring the presence and frequency of T cells specific to this pMHC complex using HLA-A*02:01/pp65 tetramers serves as a vital biomarker for assessing a patient's risk of CMV reactivation and the efficacy of immunotherapeutic interventions.

Other names

NLVPMVATV-HLA-A*02:01 complexCMV pp65(495-503) peptide-MHC complexHLA-A*02:01/UL83(495-503)CMV pp65-A2 complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ T cells, leading to the release of perforins and granzymes and subsequent apoptosis of the infected host cell.