Cytomegalovirus phosphoprotein 65-derived peptide–Major Histocompatibility Complex class I complex (CMV pp65–MHC I complex)

The Cytomegalovirus (CMV) phosphoprotein 65-derived peptide–Major Histocompatibility Complex (MHC) class I complex is a primary immunological target presented on the surface of cells infected with Human Cytomegalovirus (HCMV) (Arvin et al., 2004). The pp65 protein, encoded by the UL83 gene, is the most abundant tegument protein of the virus and serves as the dominant antigen for the CD8+ cytotoxic T-lymphocyte (CTL) response (UniProt P06725). During the viral life cycle, pp65 is processed into short peptides, such as the immunodominant NLVPMVATV sequence, which are then loaded onto MHC class I molecules (most commonly HLA-A*02:01) and displayed on the cell surface. This peptide-MHC (pMHC) complex is specifically recognized by the T-cell receptors (TCRs) of CMV-specific CD8+ T cells, leading to the targeted destruction of the infected cell through the release of perforins and granzymes (Stern et al., 2019). This complex is a major focus for therapeutic intervention, particularly in the development of adoptive T-cell therapies and vaccines aimed at controlling CMV reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation (AlloVir, 2023). Additionally, the complex is a target for emerging TCR-like antibodies and bispecific molecules that seek to bypass the need for endogenous T-cell activation.

Other names

HCMV pp65-MHC I complexUL83 peptide-HLA complexCMV pp65-HLA-A*02:01 complexpp65-derived peptide-MHC class ICMV pp65-pMHC

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies leading to directed lysis of infected cells and cytokine production.