Cytomegalovirus pp65-specific T cell receptor (CMV pp65 TCR)

The Cytomegalovirus (CMV) pp65-specific T cell receptor (TCR) is a heterodimeric surface protein that mediates the recognition of the CMV tegument protein pp65, also known as UL83 (PubMed: 15507654). This recognition is restricted by Major Histocompatibility Complex (MHC) class I molecules, most frequently the HLA-A*02:01 allele presenting the immunodominant NLVPMVATV peptide (PubMed: 10807508). In therapeutic development, these TCRs are often isolated or expanded using dendritic cells pulsed with pp65 peptides to ensure high specificity for CMV-infected cells (PubMed: 19144678). Upon binding to the peptide-MHC complex, the TCR initiates a signaling cascade that leads to T cell activation and the targeted destruction of infected cells via the release of cytotoxic molecules like granzymes and perforin. This target is primarily utilized in adoptive cell therapies, such as TCR-engineered T cells (TCR-T), to treat refractory CMV infections in immunocompromised patients, particularly post-transplant (ClinicalTrials.gov: NCT02398695). Additionally, the expression of pp65 in certain tumors, such as glioblastoma multiforme, has positioned this TCR as a candidate for targeted cancer immunotherapy.

Other names

CMV-specific TCRpp65-specific TCRHLA-A*02:01-restricted CMV pp65 TCRUL83-specific T cell receptorTCR recognizing CMV pp65 epitope

Adoptive T-cell therapy; the TCR recognizes the pp65 peptide-MHC class I complex on infected or malignant cells, triggering T-cell activation and cytotoxic lysis of the target cell.