HLA-DQ2.5-restricted gluten-specific T-cell receptor (DQ2.5-restricted TCR)

The HLA-DQ2.5-restricted 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. This receptor specifically identifies deamidated gluten peptides when they are presented by the HLA-DQ2.5 major histocompatibility complex (MHC) class II molecule on the surface of antigen-presenting cells (Sollid et al., 2013, Nature Reviews Immunology). In individuals with Celiac disease, the binding of this TCR to the gluten-HLA complex triggers a cascade of immune reactions, including the release of inflammatory cytokines such as interferon-gamma and interleukin-21, which cause damage to the small intestinal mucosa (Christophersen et al., 2014, Scientific Reports). Because this interaction is the primary driver of the disease's immune response, it is a high-priority target for therapeutic intervention. Experimental treatments like Nexvax2 and TAK-101 aim to modify the behavior of these T cells, either by inducing immune tolerance or by preventing their activation entirely (Daveson et al., 2020, The Lancet Gastroenterology & Hepatology). Successfully modulating these TCRs could potentially allow patients to consume gluten without experiencing the characteristic autoimmune destruction of the gut lining.

Other names

Gluten-specific T-cell receptorCeliac disease-associated T-cell receptorDQ2.5-glia-specific TCRGluten-reactive CD4+ T-cell receptor

Antigen-specific immunotherapy (ASIT) designed to induce immune tolerance or anergy in gluten-reactive CD4+ T cells by engaging the TCR with specific gluten epitopes in the absence of inflammatory co-stimulation.