T-cell receptor recognizing Varicella-Zoster Virus glycoprotein E-derived peptides on MHC class I (VZV gE-TCR)

T-cell receptors (TCRs) recognizing glycoprotein E (gE)-derived peptides on MHC class I molecules are essential mediators of the cytotoxic immune response against Varicella-Zoster Virus (VZV) (Arvin, 1996, Clinical Microbiology Reviews). Glycoprotein E is the most prevalent VZV surface protein and is vital for viral replication and cell-to-cell spread (Steain et al., 2014, Journal of Virology). These TCRs enable CD8+ T cells to identify and eliminate VZV-infected cells by recognizing specific gE epitopes, such as the HLA-A*02:01-restricted peptide gE 256-264, presented on the cell surface (Abendroth et al., 2001, Journal of Virology). This interaction is a primary target for the Shingrix vaccine, which utilizes a recombinant gE antigen to elicit robust T-cell mediated immunity to prevent herpes zoster (Cunningham et al., 2016, NEJM). Beyond vaccination, these TCRs are being investigated for use in adoptive T-cell transfer (ACT) to provide immunity to immunocompromised patients at risk of severe VZV-related complications (Gershon et al., 2015, The Lancet).

Other names

VZV gE-specific T-cell receptorGlycoprotein E-specific TCRAnti-VZV gE CD8+ TCRVZV gE-restricted T-cell receptor

The mechanism involves the specific binding of the T-cell receptor to a complex formed by an MHC class I molecule and a peptide fragment derived from VZV glycoprotein E. This binding triggers a signaling cascade through the CD3 complex, leading to the activation of the CD8+ T cell. The activated T cell then releases cytotoxic granules containing perforin and granzymes, which induce programmed cell death in the infected target cell, thereby limiting viral replication and spread (Abendroth et al., 2001, Journal of Virology).