Gluten peptide–Human Leukocyte Antigen DQ2.5 complex (Gluten–HLA-DQ2.5)

The Gluten peptide–Human Leukocyte Antigen DQ2.5 complex (Gluten–HLA-DQ2.5) on liver sinusoidal endothelial cells (LSECs) is a specialized immunological target utilized for inducing antigen-specific immune tolerance in Celiac disease (Takeda, 2019). In patients with Celiac disease, the immune system mounts an inappropriate response against deamidated gluten peptides presented by HLA-DQ2.5 molecules on antigen-presenting cells in the small intestine (Sollid, 2002). By contrast, when these same gluten peptides are presented by LSECs in the liver—a naturally tolerogenic environment—they promote the development of regulatory T cells or the deletion of effector T cells (Knolle & Limmer, 2001). Therapeutic candidates like TAK-101 (formerly CNP-101) consist of gliadin-containing nanoparticles designed to be scavenged by LSECs to exploit this pathway (Cour Pharmaceuticals, 2023). This approach aims to reprogram the immune system to tolerate gluten, thereby preventing the inflammatory cascade and intestinal damage characteristic of the disease (Sollid et al., 2021). Successful targeting of this complex represents a shift from symptom management via a gluten-free diet to a potential disease-modifying therapy.

Other names

Deamidated gliadin peptide-HLA-DQ2.5 complexDGP-HLA-DQ2.5MHC II-gluten peptide complexGliadin-HLA-DQ2.5 complex

Induction of antigen-specific immune tolerance via presentation of gluten peptides by tolerogenic liver sinusoidal endothelial cells (LSECs) to gluten-reactive T cells, leading to T-cell anergy or deletion.