Human leukocyte antigen class I-human cytomegalovirus peptide complex (HLA-I/HCMV complex)

Human leukocyte antigen (HLA) class I molecules presenting human cytomegalovirus (HCMV)-derived peptides are specialized protein complexes essential for the cellular immune response against HCMV. These complexes are formed when viral proteins, such as the immunodominant tegument protein pp65 (UL83) or immediate-early protein 1 (IE1), are processed by the host cell's proteasome into short peptides and loaded onto HLA class I molecules (HLA-A, -B, or -C) within the endoplasmic reticulum (NIH, 2020). Once displayed on the cell surface, these peptide-HLA (pHLA) complexes serve as the primary targets for CD8+ cytotoxic T lymphocytes, which recognize them via specific T-cell receptors (TCRs) to initiate the destruction of infected cells (MDPI, 2022). In clinical settings, particularly following hematopoietic stem cell or solid organ transplantation, the absence of effective T-cell surveillance against these complexes leads to HCMV reactivation and severe disease. Therapeutic interventions currently focus on adoptive T-cell therapies, such as virus-specific T cells (VSTs) like posoleucel, and the development of TCR-engineered T cells or TCR-like antibodies designed to bypass viral immune evasion mechanisms and restore viral control (NIH, 2025; Blood Advances, 2024). A major challenge in targeting these complexes is the high polymorphism of HLA alleles and the potential for cross-reactivity with similar self-peptides, which can lead to off-target effects.

Other names

pHLA-HCMVpMHC-I HCMVHCMV peptide-HLA complexCMV-specific HLA-IHLA-I/HCMV peptide complex

Recognition of the peptide-HLA complex by T-cell receptors (TCRs) or TCR-like antibodies, triggering T-cell activation, secretion of cytotoxic granules such as perforin and granzymes, and subsequent apoptosis of the HCMV-infected cell (NIH, 2020; NIH, 2025).