Gliadin-specific T-cell receptor (Gliadin-specific TCR)

Gliadin-specific T-cell receptors (TCRs) are specialized immune receptors found on CD4+ T cells that play a pivotal role in the pathogenesis of Celiac disease (Sollid et al., Nature Reviews Immunology, 2000). These receptors recognize specific deamidated gliadin peptides presented by HLA-DQ2.5 or HLA-DQ8 molecules on the surface of antigen-presenting cells (Christophersen et al., Scientific Reports, 2016). Upon recognition, the TCRs trigger an inflammatory cascade involving the release of pro-inflammatory cytokines like interferon-gamma (IFN-γ), which leads to the destruction of the intestinal villi and subsequent malabsorption (Koning, Gastroenterology, 2017). As the central mediators of the autoimmune response to gluten, these TCRs are high-priority targets for antigen-specific immunotherapies. Investigational drugs such as Nexvax2, KAN-101, and TAK-101 are designed to target these specific T-cell populations to induce anergy or regulatory T-cell differentiation, thereby preventing the autoimmune response to dietary gluten without requiring broad immunosuppression (Goel et al., The Lancet Gastroenterology & Hepatology, 2017; Kelly et al., Gastroenterology, 2021).

Other names

Gluten-specific T-cell receptorGliadin-reactive T-cell receptorCeliac disease-associated T-cell receptor

Induction of antigen-specific immune tolerance, T-cell anergy, or deletion of pathogenic gliadin-reactive CD4+ T cells through controlled antigen exposure or blockade of the TCR-HLA-peptide interaction.