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The Human cytomegalovirus (HCMV) pp65(495-503)/HLA-A*02:01 complex is a prominent peptide-major histocompatibility complex (pMHC) class I target essential for immune surveillance against CMV. The complex consists of the immunodominant nonapeptide NLVPMVATV, which is derived from the tegument phosphoprotein 65 (pp65 or UL83) of CMV, presented within the peptide-binding groove of the HLA-A*02:01 molecule on the surface of infected or antigen-presenting cells. This specific complex is the primary target for cytotoxic CD8+ T lymphocytes, which recognize it via their T-cell receptors (TCRs) to initiate a cell-mediated immune response. In clinical development, the complex serves as a critical target for novel immunotherapies, including TCR-engineered T cells (TCR-T) and TCR-like antibodies designed to treat refractory CMV infections in transplant recipients. Additionally, because the pp65 protein is often expressed in glioblastoma multiforme (GBM) tumor cells, this complex is also a target for cancer vaccines and specialized adoptive cell therapies aimed at treating CMV-associated malignancies.
Specific engagement by T-cell receptors (TCRs) or TCR-like antibodies leads to the recruitment and activation of cytotoxic T lymphocytes (CTLs), resulting in the release of granzyme B and perforin to induce lysis of target cells.
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