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

Gliadin-specific T-cell receptors (TCRs) are the primary drivers of the inflammatory immune response in Celiac disease, a chronic autoimmune-like disorder (Sollid et al., 2013, Nature Reviews Immunology). These receptors are expressed on CD4+ T cells and specifically recognize deamidated gliadin peptides, which are formed when the enzyme tissue transglutaminase 2 (tTG2) modifies gluten-derived proteins in the intestinal mucosa (Kupfer & Jabri, 2012, Gastroenterology). This recognition is restricted to patients carrying the HLA-DQ2.5 or HLA-DQ8 MHC class II molecules, which present the deamidated peptides to the TCRs (Abadie et al., 2011, Annual Review of Immunology). Upon activation, these T cells secrete pro-inflammatory cytokines like interferon-gamma, leading to the destruction of the intestinal villi and malabsorption (Di Sabatino et al., 2012, The Lancet). Because these TCRs are the gatekeepers of the gluten-specific response, they are major targets for therapeutic intervention. Experimental drugs like Nexvax2 and KAN-101 aim to induce immune tolerance by repeatedly exposing these TCRs to their cognate antigens in a controlled manner, potentially allowing patients to tolerate gluten without an inflammatory response (Goel et al., 2017, Lancet Gastroenterology & Hepatology). Monitoring these T cells using MHC-peptide tetramers serves as a critical biomarker for assessing the efficacy of such antigen-specific immunotherapies (Tye-Din et al., 2010, Science Translational Medicine).

Other names

Gluten-specific T-cell receptorCeliac-associated T-cell receptorDeamidated gliadin-specific TCRGluten-reactive CD4+ T-cell receptor

Induction of antigen-specific immune tolerance or anergy in gluten-reactive CD4+ T cells.