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

The Cytomegalovirus (CMV) pp65-specific T-cell receptor (TCR) is a specialized immune receptor that recognizes the pp65 protein (also known as UL83), a dominant tegument antigen of CMV (Source: UniProt P06725). This recognition occurs when pp65-derived peptides, such as the immunodominant NLVPMVATV epitope, are presented by Major Histocompatibility Complex (MHC) molecules, most notably HLA-A*02:01, on the surface of infected cells (Source: PubMed PMID: 15905523). Upon binding, the TCR initiates a signaling cascade that activates the T cell, leading to the secretion of cytotoxic granules like perforin and granzyme, as well as pro-inflammatory cytokines to eliminate the virus (Source: PubMed PMID: 23601214). In clinical settings, this TCR is a primary focus for adoptive T-cell therapies and TCR-engineered T-cell products aimed at treating CMV reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation (Source: PubMed PMID: 31142651). The specificity of this interaction is crucial for ensuring effective viral clearance while minimizing damage to healthy tissues. Therapeutic candidates like posoleucel (ALVR105) utilize this recognition mechanism to provide broad-spectrum antiviral activity in high-risk patients (Source: AlloVir). Challenges in targeting this complex include the high polymorphism of HLA molecules and the potential for off-target cross-reactivity with self-antigens.

Other names

UL83-specific T-cell receptorpp65-HLA complex-specific TCRCMV-specific TCRpp65-specific TCR

Binding of the T-cell receptor to the pp65 peptide-MHC complex on the surface of infected cells, triggering T-cell activation, cytokine release, and targeted lysis of the CMV-infected cell.