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

The complex consisting of the Cytomegalovirus (CMV) phosphoprotein 65 (pp65) peptide NLVPMVATV and the Human Leukocyte Antigen (HLA) allele A*02:01 is a primary target for cellular immunotherapy. The pp65 protein, encoded by the UL83 gene, is a major structural component of the CMV tegument and serves as a dominant antigen for the host immune response (Wills et al., 1996, PMID: 8676462). The specific nonamer peptide NLVPMVATV (residues 495-503) is highly immunogenic and is efficiently presented by the common HLA-A*02:01 molecule to CD8+ cytotoxic T lymphocytes (Diamond et al., 1997, PMID: 9234714). In immunocompromised individuals, such as hematopoietic stem cell or solid organ transplant recipients, CMV reactivation can lead to severe morbidity and mortality. Consequently, this peptide-MHC complex is a critical target for adoptive T-cell therapies, including the infusion of ex vivo expanded CMV-specific T cells or TCR-engineered T cells. Investigational drugs like posoleucel (Viralym-M) and vaccines like Triplex leverage this epitope to restore or enhance viral control (AlloVir, 2023; City of Hope, 2024). Safety concerns primarily involve potential cross-reactivity with self-peptides and the risk of cytokine release syndrome during T-cell activation.

Other names

NLVPMVATV-HLA-A*02:01 complexCMV pp65 (495-503) epitopeHLA-A*02:01/pp65(495-503)NLV peptidepMHC complex HLA-A*02:01/NLVPMVATV

Recognition by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the targeted destruction of CMV-infected cells expressing the pp65 antigen.