Cytomegalovirus pp65 and IE-1 peptide-MHC complexes (CMV pp65/IE-1 pMHC)

Cytomegalovirus (CMV) pp65 and IE-1 peptide-MHC complexes are the primary molecular targets for the cellular immune response against CMV-infected cells. These complexes consist of short peptides derived from the immunodominant viral proteins phosphoprotein 65 (pp65, UL83) and Immediate-Early 1 (IE-1, UL123), which are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and II molecules (Human Leukocyte Antigens, HLA) [1, 3, 5]. In healthy individuals, these complexes are recognized by a robust population of memory T cells that maintain viral latency; however, in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation, the absence of these T cells leads to viral reactivation and severe end-organ diseases like retinitis or pneumonitis [12, 14, 19]. Therapeutic strategies targeting these complexes focus on restoring the host's cellular immunity through the adoptive transfer of virus-specific T cells (VSTs), such as the multi-virus product posoleucel, or through highly specific TCR-engineered T cells (TCR-T) [15, 17, 20]. Additionally, novel T-cell receptor-like (TCR-like) antibodies are being developed to provide targeted recognition and elimination of infected cells via mechanisms like antibody-dependent cellular cytotoxicity (ADCC) [10, 16]. These immunotherapies aim to provide a safer and more effective alternative to traditional antiviral drugs, which often carry significant toxicities and are prone to the development of viral resistance [18, 23].

Other names

CMV pp65/IE-1 peptide-HLA complexesCMV antigen-MHC complexesCMV-specific pMHCCytomegalovirus phosphoprotein 65 and Immediate-Early 1 peptide-MHC complexespCMV-pp65/HLA complexpCMV-IE-1/HLA complex

Adoptive transfer of virus-specific T cells (VSTs) or TCR-engineered T cells (TCR-T) that recognize these specific peptide-MHC complexes on the surface of infected cells, leading to targeted cell lysis via the release of granzymes and perforin. TCR-like antibodies can also target these complexes to mediate antibody-dependent cellular cytotoxicity (ADCC) or deliver cytotoxic payloads.