Cytomegalovirus immediate-early 1 protein-derived peptides presented by human leukocyte antigen class I (CMV IE-1/HLA-I)

The Cytomegalovirus (CMV) immediate-early 1 (IE-1) protein, also known as UL123, is one of the first viral proteins expressed upon infection or reactivation of Human Cytomegalovirus (HCMV) [1]. Peptides derived from this protein are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I molecules, where they serve as dominant targets for the host's CD8+ cytotoxic T-cell response [2]. This peptide-MHC (pMHC) complex is a critical therapeutic target for managing CMV in immunocompromised individuals, such as hematopoietic stem cell or solid organ transplant recipients, who lack effective endogenous viral control [3]. Current therapeutic strategies targeting this complex include the adoptive transfer of donor-derived or off-the-shelf CMV-specific T-cells and the development of peptide-based vaccines [4]. These therapies rely on the high specificity of the T-cell receptor (TCR) for the IE-1 peptide presented within the groove of specific HLA alleles, most commonly HLA-A*02:01 [5]. Successful targeting of the IE-1/HLA complex leads to the selective lysis of infected cells and the reduction of viral load, though challenges remain regarding HLA restriction and potential off-target effects [6]. Sources: [1] UniProt (P13202) [2] Khan et al., J Virol (2007), PubMed: 17507481 [3] Stern et al., Blood (2019), PubMed: 31315834 [4] Atara Biotherapeutics (ATA227 Product Pipeline) [5] Wieczorek et al., Front Immunol (2017), PubMed: 28360920 [6] ClinicalTrials.gov (NCT02398617)

Other names

HCMV IE1 peptide-MHC complexUL123-derived peptides presented by HLA-ICMV IE1-specific pMHCHuman cytomegalovirus immediate-early 1 antigen

Recognition of the peptide-HLA complex by the T-cell receptor (TCR) on CD8+ T-cells, triggering the release of perforins and granzymes to induce apoptosis in infected cells.