Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity-Reference-Cited by-全球学者库

Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity

Published:2023-03-17 Issue:6637 Volume:379 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zhai Yue¹^ORCID,Chen Liang²^ORCID,Zhao Qian³^ORCID,Zheng Zhao-Hui¹^ORCID,Chen Zhi-Nan¹^ORCID,Bian Huijie¹^ORCID,Yang Xu¹,Lu Huan-Yu⁴,Lin Peng¹^ORCID,Chen Xi¹^ORCID,Chen Ruo¹,Sun Hao-Yang¹,Fan Lin-Ni⁵^ORCID,Zhang Kun¹,Wang Bin¹,Sun Xiu-Xuan¹,Feng Zhuan¹,Zhu Yu-Meng¹,Zhou Jian-Sheng¹^ORCID,Chen Shi-Rui¹,Zhang Tao¹,Chen Si-Yu¹,Chen Jun-Jie¹,Zhang Kui¹,Wang Yan¹,Chang Yang¹,Zhang Rui¹,Zhang Bei¹^ORCID,Wang Li-Juan¹,Li Xiao-Min¹,He Qian¹,Yang Xiang-Min¹,Nan Gang¹,Xie Rong-Hua¹^ORCID,Yang Liu¹,Yang Jing-Hua¹³^ORCID,Zhu Ping¹^ORCID

Affiliation:

1. Department of Clinical Immunology, Xijing Hospital, and Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, China.

2. School of Medicine, Shanghai University, Shanghai 200444, China.

3. Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China.

4. Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an 710032, China.

5. State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.abg2482

Reference59 articles.

1. Immune tolerance and autoreactivity: Do they point to a regulatory role of the immune system for normal cell function?

2. Homeostasis and Self-Tolerance in the Immune System: Turning Lymphocytes off

3. ACPA status influences RA development

4. ACPA mediates the interplay between innate and adaptive immunity in rheumatoid arthritis

5. Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis

Cited by 19 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Metabolomic landscape of macrophage discloses an anabolic signature of dengue virus infection and antibody-dependent enhancement of viral infection;PLOS Neglected Tropical Diseases;2024-02-02

2. Mass Spectrometry Analysis on the Breakage of Allergens in High-Molecular-Mass Polymer of Roasted Peanuts;Journal of Agricultural and Food Chemistry;2024-02-01

3. Breaking tolerance: autoantibodies can target protein posttranslational modifications;Current Opinion in Biotechnology;2024-02

4. T cells in the pathogenesis of axial spondyloarthritis;Joint Bone Spine;2023-12

5. Abundance of human T-cell epitopes in microbial proteomes;2023-11-30