Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis.

ABSTRACT: Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized to drive the loss of immune tolerance to self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune responses to citrullinated self-antigens, in which arginine residues are converted to citrullines. Here, we investigate the hypothesis that citrullination exposes cryptic peptides by modifying protein structure and proteolytic cleavage. We show that citrullination alters processing and presentation of autoantigens, resulting in the generation of a unique citrullination-dependent repertoire composed primarily of native sequences. This repertoire stimulates T cells from RA patients with anti-citrullinate

SUBMITTER: Curran AM 

PROVIDER: S-EPMC9958131 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature