LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.

ABSTRACT: Celiac disease (CeD) is an autoimmune disorder in which gluten-derived antigens trigger inflammation. Antigenic peptides must undergo site-specific deamidation to be presentable to CD4⁺ T cells in an HLA-DQ2 or -DQ8 restricted manner. While the biochemical basis for this post-translational modification is understood, its localization in the patient's intestine remains unknown. Here, we describe a mechanism by which gluten peptides undergo deamidation and concentration in the lysosomes of antigen-presenting cells, explaining how the concentration of gluten peptides necessary to elicit an inflammatory response in CeD patients is achieved. A ternary complex forms between a gluten peptide, transglutaminase-2 (TG2), and ubiquitous plasma protein α₂-macroglobulin, and is en

SUBMITTER: Loppinet E 

PROVIDER: S-EPMC9868102 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature