T-cell receptor recognizing Tick-borne encephalitis virus peptides presented on HLA class I (TBEV-specific TCR)

Human CD8+ T-cell receptors (TCRs) specific for Tick-borne encephalitis virus (TBEV) are essential components of the adaptive immune system responsible for identifying and eliminating cells infected with the virus (Blom et al., 2015, PLOS Pathogens). These receptors recognize short viral peptide fragments, frequently derived from non-structural proteins like NS3 (e.g., the HLA-A*02:01 restricted epitope NS3_1616), which are presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules (Lindgren et al., 2021, Journal of Virology). Upon recognition, the TCR complex initiates a signaling cascade that activates the CD8+ T cell to perform effector functions, including the secretion of cytotoxic molecules and antiviral cytokines like IFN-gamma (NCBI, 2023). In the context of TBEV infection, a robust and specific TCR response is associated with effective viral clearance and protection against severe neurological complications such as encephalitis and meningitis (Ruzek et al., 2019, Antiviral Research). These TCRs are currently being investigated for their potential in developing TCR-engineered T-cell (TCR-T) therapies for immunocompromised patients and for refining vaccine strategies to elicit more durable cellular immunity. Understanding the structural basis of the TCR-pMHC interaction is critical for predicting potential cross-reactivity and ensuring the safety of therapeutic interventions targeting this pathway.

Other names

Tick-borne encephalitis virus-specific T-cell receptorTBEV-specific CD8+ TCRHLA-restricted TBEV TCRTBEV-specific T-cell receptor

The T-cell receptor (TCR) complex specifically recognizes TBEV-derived peptide fragments (epitopes), such as those from the NS3 or Envelope proteins, displayed by HLA class I molecules on the surface of infected cells. This binding event, stabilized by the CD8 co-receptor, triggers intracellular signaling via CD3 ITAM phosphorylation and ZAP-70 activation, leading to the release of cytotoxic granules (perforin and granzymes) and pro-inflammatory cytokines like IFN-gamma, which collectively induce apoptosis in the virus-infected cell (Blom et al., 2015; Lindgren et al., 2021).