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A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes

Proc Natl Acad Sci U S A. 2022-07; 
Khyati Girdhar, Qian Huang, I-Ting Chow, Tommi Vatanen, Claudia Brady, Amol Raisingani, Patrick Autissier, Mark A Atkinson, William W Kwok, C Ronald Kahn, Emrah Altindis
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摘要

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of autoantibodies and T cells directed at an epitope in the B-chain of insulin (insB:9-23). Analysis of microbial protein sequences with homology to the insB:9-23 sequence revealed 17 peptides showing >50% identity to insB:9-23. Of these 17 peptides, the peptide, found in the normal human gut commensal , activated both human T cell clones from T1D patients and T cell hybridomas from nonobese diabetic (NOD) mice specific to insB:9-23. Immunization of NOD mice with insB:9-23 peptide mimic or insB:9-23 peptide verified immune cross-reactivity. Colo... More

关键词

Parabacteroides distasonis, gut microbiome, insB:9-23 epitope, molecular mimicry, type 1 diabetes
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