Cytomegalovirus phosphoprotein 65-derived peptide–Major Histocompatibility Complex (CMV pp65-pMHC)

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is the most abundant tegument protein of human cytomegalovirus (HCMV) and a primary target of the host's cellular immune response (UniProt P06725). During infection or in certain tumors, pp65 is processed into short peptides that are loaded onto Major Histocompatibility Complex (MHC) Class I molecules for presentation on the cell surface. The most well-characterized epitope is the NLVPMVATV peptide presented by HLA-A*02:01, which is recognized by high-avidity CD8+ T-cell receptors (PubMed: 15604134). These pMHC complexes are critical therapeutic targets in the management of CMV reactivation in hematopoietic stem cell transplant (HSCT) and solid organ transplant recipients. Additionally, the presence of pp65 in glioblastoma cells has led to the development of TCR-engineered T cells and vaccines aimed at these specific complexes to treat CNS malignancies (PubMed: 25762132). Therapeutic strategies include adoptive transfer of CMV-specific T cells and the use of bispecific molecules that bridge the pMHC complex with T-cell activating receptors.

Other names

CMV pp65-MHC complexpp65 peptide-HLA complexNLVPMVATV-HLA-A*02:01 complexHCMV pp65-pMHCUL83 peptide-MHC complex

The mechanism involves the recognition of the specific pp65 peptide (e.g., NLVPMVATV) presented within the groove of an MHC molecule (e.g., HLA-A*02:01) by a cognate T-cell receptor (TCR). This interaction forms an immunological synapse, triggering the release of perforin and granzymes from the T cell, which induces apoptosis in the target cell (PubMed: 15604134). In the case of vaccines, the pMHC complex is formed on endogenous antigen-presenting cells to prime and expand the pool of CMV-specific memory T cells.