Cytomegalovirus 65 kDa phosphoprotein peptide presented on Human leukocyte antigen class I (CMV pp65/HLA-I)

Cytomegalovirus 65 kDa phosphoprotein (pp65), encoded by the UL83 gene, is the most abundant tegument protein of Human Cytomegalovirus (HCMV) and serves as a dominant antigen for the host's cellular immune response (UniProt P06725). During infection, pp65 is processed into short peptides that are presented on the cell surface by Human leukocyte antigen (HLA) class I molecules for recognition by CD8+ cytotoxic T lymphocytes (CTLs) [1.1.3, 1.4.3]. The NLVPMVATV peptide, typically presented by the HLA-A*02:01 allele, is a highly immunogenic epitope that often dominates the CMV-specific T-cell repertoire in seropositive individuals [1.2.2, 1.4.1]. This peptide-HLA complex is a primary therapeutic target for managing CMV reactivation in immunocompromised patients, such as hematopoietic stem cell or solid organ transplant recipients [1.1.2, 1.4.2]. Current therapeutic strategies include the adoptive transfer of donor-derived CMV-specific T cells (VSTs), the development of TCR-engineered T cells (TCR-T), and vaccines like Triplex that aim to boost endogenous immunity [1.1.2, 1.4.4]. Additionally, novel TCR-like antibodies and bispecific molecules are being engineered to specifically target cells displaying these viral antigens to mediate their destruction [1.1.1, 1.1.3]. Monitoring the presence of this target and the corresponding T-cell response is essential for clinical assessment of viral control and the efficacy of immunotherapy [1.2.2].

Other names

CMV pp65 peptide-MHC complexUL83 peptide-HLA complexpp65/HLA-A*02:01NLVPMVATV/HLA-A*02:01 complexCMV pp65 pMHCCytomegalovirus pp65 peptide-HLA class I complex

Recognition of the specific peptide-HLA complex by T-cell receptors (TCRs) or TCR-like antibodies, which triggers the activation of cytotoxic T-lymphocytes (CTLs) and subsequent lysis of the target cell through the release of perforin and granzymes.