T-cell receptor specific for Cytomegalovirus pp65 peptide-HLA complex (CMV-pp65-specific TCR)

The T-cell receptor (TCR) on host CD8+ T cells specific for the Cytomegalovirus (CMV) pp65 peptide-HLA complex is a pivotal mediator of the cellular immune response against CMV. CMV is a widespread beta-herpesvirus that establishes lifelong latency and can lead to life-threatening complications in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation (Wills et al., 1996, PMID: 8676462). The pp65 protein, encoded by the UL83 gene, is the most abundant tegument protein and serves as the primary immunodominant antigen for CD8+ T cells (Arvin et al., 2004, PMID: 15507154). Upon recognition of the pp65 peptide (most notably the NLVPMVATV epitope) presented by HLA-A*02:01 on the surface of infected cells or professional antigen-presenting cells like dendritic cells, the TCR initiates a signaling cascade leading to T-cell activation and proliferation. This activation results in the release of perforin and granzymes to induce apoptosis in the target cell, effectively controlling viral spread (Schub et al., 2009, PMID: 19155473). This receptor is a major focus for therapeutic intervention, particularly in adoptive T-cell transfer (ACT) and TCR-engineered T-cell therapies, which aim to restore CMV-specific immunity in patients at risk of viral reactivation (NCT02307331). Clinical challenges include the necessity for HLA-matching between the therapy and the patient, as well as the potential for cytokine release syndrome or graft-versus-host disease in allogeneic settings.

Other names

CMV-specific T-cell receptorpp65-specific TCRNLVPMVATV-specific TCRCMV-pp65-HLA-A*02:01-specific TCR

Antigen-specific T-cell activation and cytotoxic elimination of CMV-infected cells