Cytomegalovirus peptide-Human Leukocyte Antigen complexes (CMV pMHC)

Cytomegalovirus (CMV) peptide-Human Leukocyte Antigen (HLA) complexes are critical molecular targets on the surface of cells infected with Human Cytomegalovirus (HCMV). These complexes consist of viral peptides, most notably from the immunodominant proteins pp65 (UL83) and IE-1 (UL123), presented by HLA class I molecules such as HLA-A*02:01. The NLVPMVATV (pp65) and VLEETSVML (IE-1) epitopes are among the most frequently recognized by the host's CD8+ T-cell repertoire, serving as the primary signal for immune-mediated viral control. In immunocompromised individuals, such as hematopoietic stem cell or solid organ transplant recipients, the failure of the immune system to recognize these complexes leads to viral reactivation and severe systemic disease. Therapeutic strategies targeting these pMHC complexes include the adoptive transfer of CMV-specific T cells (VSTs), TCR-engineered T cells (TCR-T), and TCR-like antibodies (TCRm), which aim to restore or enhance the cytotoxic elimination of infected cells. However, therapeutic challenges include viral immunoevasins that downregulate HLA expression and potential cross-reactivity with self-peptides that may trigger graft-versus-host disease.

Other names

Cytomegalovirus peptide-MHC complexesCMV pMHCHLA-A*02:01-NLVPMVATVHLA-A*02:01-VLEETSVMLCMV-pp65(495-503)/HLA-A*02:01CMV-IE-1(316-324)/HLA-A*02:01pp65/UL83 epitopeIE-1/UL123 epitope

Recognition of the specific peptide-HLA complex by T-cell receptors (TCRs) or TCR-like antibodies, triggering the activation of cytotoxic T-cells and the subsequent release of perforin and granzymes to induce apoptosis in CMV-infected cells.