Cytomegalovirus pp65-derived peptide-MHC class I complex (CMV pp65-pMHC I)

The Cytomegalovirus (CMV) pp65-derived peptide presented on MHC class I is a primary immunological target for managing CMV infection and certain malignancies. The pp65 protein, also known as UL83, is the most abundant tegument protein of Human Cytomegalovirus (HCMV) and is highly immunodominant, eliciting robust CD8+ T-cell responses (UniProt P06725; Wills et al., 1996, J. Virol.). During infection or in certain tumors, pp65 is processed into short peptides, such as the immunodominant NLVPMVATV epitope, which are then presented on the cell surface by MHC class I molecules like HLA-A*02:01 (Boeckh & Ljungman, 2009, Blood). This peptide-MHC (pMHC) complex is recognized by the T-cell receptors (TCRs) of CD8+ T cells, triggering an immune response that leads to the destruction of the target cell. In clinical settings, this target is utilized in adoptive cell therapies, such as Viralym-M, which infuse donor-derived CMV-specific T cells into immunocompromised patients to restore viral immunity (AlloVir, 2023). Furthermore, the expression of pp65 in glioblastoma multiforme has made this pMHC complex a target for therapeutic vaccines and TCR-engineered T-cell therapies in oncology (Mitchell et al., 2015, Nature). The specificity of the TCR-pMHC interaction is a cornerstone of precision immunotherapy, aimed at clearing CMV-positive cells while minimizing off-target effects.

Other names

CMV pp65 antigenUL83-derived peptide-MHC complexHLA-A*02:01-restricted NLVPMVATV peptideCytomegalovirus 65 kDa phosphoprotein-MHC complexCMV pp65-HLA complex

T-cell receptor (TCR) mediated recognition and cytotoxic T-lymphocyte (CTL) activation leading to targeted lysis of CMV-infected or pp65-expressing cells.