Details

Autor(en) / Beteiligte

• Zhai, Yue
• Chen, Liang
• Zhao, Qian
• Zheng, Zhao-Hui
• Chen, Zhi-Nan
• Bian, Huijie
• Yang, Xu
• Lu, Huan-Yu
• Lin, Peng
• Chen, Xi
• Chen, Ruo
• Sun, Hao-Yang
• Fan, Lin-Ni
• Zhang, Kun
• Wang, Bin
• Sun, Xiu-Xuan
• Feng, Zhuan
• Zhu, Yu-Meng
• Zhou, Jian-Sheng
• Chen, Shi-Rui
• Zhang, Tao
• Chen, Si-Yu
• Chen, Jun-Jie
• Zhang, Kui
• Wang, Yan
• Chang, Yang
• Zhang, Rui
• Zhang, Bei
• Wang, Li-Juan
• Li, Xiao-Min
• He, Qian
• Yang, Xiang-Min
• Nan, Gang
• Xie, Rong-Hua
• Yang, Liu
• Yang, Jing-Hua
• Zhu, Ping

Titel

Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity

Ist Teil von

• Science (American Association for the Advancement of Science), 2023-03, Vol.379 (6637), p.eabg2482-eabg2482

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2023

Link zum Volltext

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4 T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4 T cell responses and autoantibody production in autoimmune diseases.