Cytomegalovirus pp65 peptide-HLA class I complex (CMV pp65-HLA-I complex)

The Cytomegalovirus pp65 peptide-HLA class I complex is a specific molecular assembly found on the surface of cells infected with Human Cytomegalovirus (HCMV). It consists of an 8-11 amino acid peptide derived from the viral phosphoprotein 65 (pp65), the most abundant internal matrix protein of CMV (UniProt P06725), bound within the groove of a Class I Major Histocompatibility Complex (MHC) molecule. This complex serves as a critical signal for the immune system, specifically allowing CD8+ cytotoxic T lymphocytes to identify and eliminate virally infected cells through the recognition of the immunodominant NLVPMVATV epitope presented by HLA-A*02:01 (PubMed: 10438930). In clinical settings, this complex is a primary target for adoptive T-cell therapies and TCR-engineered T cells, particularly in immunocompromised patients such as hematopoietic stem cell or solid organ transplant recipients who suffer from refractory CMV infection (PubMed: 26034293). Therapeutic strategies aim to bypass or augment the host's natural immune response by providing T cells that specifically recognize this pMHC complex. Monitoring the presence of this target and the patient's HLA type is essential for the efficacy of these precision immunotherapies, as the virus can employ evasion tactics like downregulating HLA expression to avoid detection.

Other names

CMV pp65-MHC complexHLA-A*02:01/pp65(NLVPMVATV) complexHuman cytomegalovirus phosphoprotein 65-HLA complexpMHC complex (CMV pp65)

Therapeutic agents, such as CMV-specific T cells or TCR-engineered cells, utilize their T-cell receptors to specifically bind the pp65 peptide-HLA complex on the surface of infected cells. This binding event triggers the formation of an immunological synapse, leading to the directed secretion of cytotoxic granules (perforin and granzymes) and the induction of apoptosis in the target cell (PubMed: 26034293).