Cytomegalovirus antigen-derived peptide–Major Histocompatibility Complex class I complex (CMV peptide–MHC I complex)

Cytomegalovirus (CMV) antigen-derived peptide–Major Histocompatibility Complex (MHC) class I complexes are molecular assemblies consisting of a host MHC class I molecule (HLA in humans) and a short peptide fragment derived from CMV proteins, such as pp65 (UL83) or IE1 (UL123). These complexes are expressed on the surface of infected cells and serve as the primary ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs), which are crucial for controlling CMV infection (Reddehase, 2002, Nature Reviews Immunology). In immunocompromised individuals, such as hematopoietic stem cell transplant (HSCT) recipients, the failure of this T-cell recognition leads to viral reactivation and severe disease (Stern et al., 2019, Blood). Therapeutic approaches targeting these complexes include vaccines designed to present multiple CMV antigens to the immune system (e.g., Triplex) and adoptive T-cell therapies (e.g., posoleucel) that utilize donor-derived T cells specific for these pMHC combinations (La Rosa et al., 2017, Blood; AlloVir, 2023, Company Website). The inclusion of additional antigens beyond the immunodominant pp65 aims to broaden the protective immune response and overcome viral strategies that downregulate specific MHC molecules to evade detection.

Other names

CMV pMHC IHCMV peptide-HLA class I complexCytomegalovirus-specific MHC-peptide complexCMV-specific pMHCHLA-CMV peptide complex

These complexes act as the specific recognition elements for CD8+ T-cell receptors (TCRs). Therapeutic strategies involve using these complexes to stimulate endogenous T-cell expansion (vaccines) or using them to select and expand donor-derived T cells for adoptive transfer to treat or prevent CMV disease in immunocompromised patients.