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The CMV pp65 peptide–Major Histocompatibility Complex (CMV pp65-MHC) is a molecular assembly on the surface of cells that serves as a primary target for the cellular immune response against human cytomegalovirus (HCMV) [1.2.4]. It consists of a peptide fragment derived from the immunodominant tegument protein pp65 (also known as UL83) bound to a Major Histocompatibility Complex (MHC) molecule, typically HLA-A*02:01 [1.3.2, 1.3.4]. In healthy individuals, these complexes are recognized by CD8+ cytotoxic T cells, which maintain viral latency; however, in immunocompromised patients, such as transplant recipients, the failure of this recognition leads to life-threatening CMV reactivation [1.2.1, 1.4.3]. Beyond infectious disease, these complexes are also found on the surface of certain tumor cells, notably in glioblastoma, where they are exploited as targets for immunotherapy [1.3.3, 1.4.2]. Therapeutic strategies include peptide vaccines, adoptive T-cell transfers, and TCR-like antibodies designed to trigger the destruction of cells presenting these viral antigens [1.3.2, 1.3.4]. These interventions aim to restore or enhance the immune system's ability to identify and eliminate cells harboring the virus or expressing its proteins [1.1.2].
Recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-like antibodies, leading to the activation of cytotoxic T lymphocytes (CTLs) and subsequent lysis of the target cell [1.2.4, 1.3.2].
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