Cytomegalovirus pp65 and IE1 peptide-Major Histocompatibility Complex class I complex (CMV pp65/IE1 pMHC-I)

The Cytomegalovirus (CMV) pp65 and IE1 peptide-Major Histocompatibility Complex (MHC) class I complex is a molecular assembly presented on the surface of cells infected with Human Betaherpesvirus 5 [1]. These complexes consist of immunodominant viral epitopes derived from the phosphoprotein 65 (pp65) and immediate-early 1 (IE1) proteins, which are processed and loaded onto MHC class I molecules for recognition by the adaptive immune system [2]. Their primary biological function is to serve as the specific ligand for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, thereby initiating the destruction of infected cells [3]. In clinical practice, these complexes are the primary targets for adoptive T-cell therapies and TCR-engineered T cells (TCR-T) designed to treat or prevent CMV disease in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation [4]. CMV infection remains a major cause of morbidity in these populations, leading to complications like pneumonia and retinitis [5]. Therapeutic success depends on the precise recognition of these pMHC complexes, though challenges such as HLA polymorphism and viral immune evasion through MHC downregulation persist [1, 4].

Other names

Cytomegalovirus pp65/IE1-HLA complexCMV antigen-MHC complexHLA-A*02:01-NLVPMVATV complexHLA-A*02:01-VLEETSVML complexCMV pMHC-I

Recognition of the specific viral peptide-MHC complex by the T-cell receptor (TCR) of cytotoxic CD8+ T cells, triggering immunological synapse formation, release of perforins and granzymes, and subsequent lysis of the infected cell [3, 4].