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

The gluten-specific T cell receptor (TCR) is a specialized protein complex found on the surface of CD4+ T cells that plays a central role in the development of Celiac disease. These receptors are responsible for the recognition of deamidated gluten peptides, which are formed when the enzyme tissue transglutaminase 2 (TG2) modifies gluten-derived gliadin in the small intestine (Sollid et al., 2013). In individuals with the HLA-DQ2 or HLA-DQ8 genotype, these peptides are presented to the gluten-specific TCR, initiating an inflammatory cascade characterized by the release of interferon-gamma and other cytokines (Christophersen et al., 2014). This immune activation leads to the destruction of the intestinal lining, resulting in villous atrophy and various systemic symptoms. Because these TCRs are highly specific to the disease-causing agent, they represent an ideal target for antigen-specific immunotherapies. Current drug development efforts, such as TAK-101 and KAN-101, focus on inducing immune tolerance by presenting gluten antigens to these receptors in a way that promotes T cell exhaustion or the formation of regulatory T cells (Kelly et al., 2021). This approach aims to prevent the autoimmune-like attack upon gluten exposure without compromising the rest of the immune system (Goel et al., 2017).

Other names

Gliadin-specific T cell receptorDeamidated gluten peptide-specific TCRCeliac disease-associated T cell receptor

Induction of antigen-specific immune tolerance and T-cell anergy or deletion of pathogenic gluten-reactive T cells.