T-cell receptor recognizing Ebola virus glycoprotein epitopes presented by MHC (EBOV-GP-specific TCR)

The T-cell receptor (TCR) recognizing Ebola virus glycoprotein (EBOV-GP) epitopes presented by the Major Histocompatibility Complex (MHC) is a pivotal mediator of cellular immunity against Ebola Virus Disease (EVD). These receptors, expressed on the surface of T lymphocytes, specifically bind to viral peptide fragments—such as the immunodominant GP-577-585 epitope—displayed by human leukocyte antigen (HLA) molecules like HLA-A*02:01 [1, 3]. This recognition event is essential for the activation of CD8+ cytotoxic T cells and CD4+ helper T cells, which coordinate the destruction of infected cells and the production of protective cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) [9, 20]. Therapeutic strategies, including the FDA-approved vaccines Ervebo and Zabdeno/Mvabea, function by inducing the expansion of these antigen-specific TCR-bearing T cells to provide long-term protection [12, 22]. Additionally, experimental TCR-engineered T-cell (TCR-T) therapies are being explored to provide passive cellular immunity by transferring T cells equipped with high-affinity TCRs specific for EBOV-GP [20, 31]. However, the virus employs sophisticated evasion tactics, such as the steric masking of MHC-I molecules by the heavily glycosylated glycoprotein, which can physically block TCR access and impair immune clearance [8, 29]. Understanding the specificity and affinity of these TCR-epitope interactions is crucial for designing next-generation vaccines and immunotherapies capable of overcoming viral escape and ensuring broad population coverage [6, 11, 33].

Other names

Ebola virus glycoprotein-specific T-cell receptorEBOV-GP TCRT-cell receptor recognizing EBOV-GP/MHC complexGlycoprotein-specific T-cell receptor

Induction of antigen-specific T-cell expansion and memory; Adoptive transfer of antigen-specific cytotoxic T cells; Targeted lysis of infected cells via TCR-pMHC recognition