Cytomegalovirus phosphoprotein 65 (pp65) and immediate-early 1 (IE1) peptides presented on HLA class I (CMV pp65/IE1-HLA)

The Cytomegalovirus (CMV) phosphoprotein 65 (pp65, encoded by UL83) and Immediate-Early 1 (IE1, encoded by UL123) proteins are major immunodominant antigens recognized by the human immune system during infection [UniProt P06725, P13202]. These viral proteins are processed into short peptide fragments and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, forming a peptide-MHC complex [Hewitt, E. W. (2003), Immunology]. This complex is the specific target for CD8+ cytotoxic T lymphocytes (CTLs), which play a critical role in controlling CMV replication and preventing clinical disease [Wills, M. R., et al. (1996), Journal of Virology]. In patients with compromised immune systems, such as those undergoing hematopoietic stem cell or solid organ transplantation, the absence of a robust T-cell response against these epitopes can lead to life-threatening CMV reactivation [Stern et al. (2019), American Journal of Transplantation]. Therapeutic strategies targeting these complexes include the adoptive transfer of ex vivo expanded CMV-specific T cells and the administration of vaccines, such as the Triplex vaccine, designed to stimulate endogenous T-cell production [Diamond, D. J., et al. (2018), Blood]. These approaches aim to provide highly specific antiviral activity while minimizing the toxicities associated with conventional small-molecule antivirals like ganciclovir [Chemaly, R. F., et al. (2019), Blood].

Other names

CMV pp65CMV IE1UL83UL123CMV MHC-I epitopesCMV peptide-MHC complexNLVPMVATV-HLA-A*02:01 complex

T-cell receptor (TCR) recognition of the peptide-MHC complex leads to the activation of CD8+ cytotoxic T lymphocytes, which subsequently induce apoptosis in CMV-infected cells through the release of perforin and granzymes.