TCR-like antibodies tackle celiac disease

Abstract

Immunotherapy Ingestion of gluten-containing food triggers the gastrointestinal symptoms of celiac disease in patients with CD4+ T cells specific for deamidated gluten peptides presented by cells. Frick et al. used phage display technology to screen for T cell receptor (TCR)–like antibodies specific for an immunodominant gluten peptide bound by the protein HLA-DQ2.5. Antibody engineering optimized affinity and binding stability, yielding an improved TCR-like antibody that structurally mimicked the TCR interface with gluten peptide–protein complexes. These TCR-like antibodies blocked the activation and proliferation of gluten-responsive human CD4+ T cells both in vitro and in DQ2.5-transgenic mice. TCR-like antibodies that block immunodominant epitope recognition have potential as personalized treatments for blunting gluten-activated T cell responses without compromising the effector functions provided by other T cells. Sci. Immunol. 6 , eabg4925 (2021).