Gluten-reactive CD4+ T cell receptor (Gluten-reactive TCR)

Gluten-reactive CD4+ T cell receptors (TCRs) are membrane-bound heterodimers expressed on the surface of T lymphocytes that play a pivotal role in the pathogenesis of Celiac disease (Sollid et al., Nature Reviews Immunology, 2013). These receptors specifically recognize deamidated gluten peptides when presented by human leukocyte antigen (HLA) molecules, primarily HLA-DQ2.5 and HLA-DQ8, on the surface of antigen-presenting cells (Christophersen et al., Scientific Reports, 2016). Upon recognition, these T cells become activated and orchestrate an inflammatory response characterized by the release of pro-inflammatory cytokines like interferon-gamma, leading to intestinal tissue damage and villous atrophy (Jabri & Sollid, Gastroenterology, 2017). Because these TCRs are the primary drivers of the abnormal immune response to dietary gluten, they are key targets for antigen-specific immunotherapies (Goel et al., The Lancet Gastroenterology & Hepatology, 2017). Therapeutic approaches such as Nexvax2 and KAN-101 aim to reprogram the immune system to tolerate gluten by specifically engaging these receptors under non-inflammatory conditions (Lutter et al., Frontiers in Immunology, 2022). Successfully modulating these TCRs could allow Celiac patients to consume gluten without triggering an adverse immune reaction (Tye-Din et al., Science Translational Medicine, 2010).

Other names

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

Antigen-specific immunotherapy designed to induce immune tolerance or desensitization of gluten-reactive T cells through controlled exposure to gluten epitopes (Goel et al., 2017).