Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context
Summary: Background: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and...
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Elsevier
2025-01-01
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| author | Xin Ma Jian Zhang Qianling Jiang Yong-Xin Li Guan Yang |
| author_facet | Xin Ma Jian Zhang Qianling Jiang Yong-Xin Li Guan Yang |
| author_sort | Xin Ma |
| collection | DOAJ |
| description | Summary: Background: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction. Methods: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens. Subsequently, we conducted a range of in vitro and in vivo assays to assess the encephalitogenic potential of these microbial-derived peptides. Findings: We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) shows the ability to activate MOG35-55-specific CD4+ T cells in vitro. Furthermore, P3 shows encephalitogenic capacity and has the potential to induce EAE in some animals. Notably, mice immunized with a combination of P3 and MOG35-55 develop severe EAE. Additionally, dendritic cells could process and present P3 to MOG35-55-specific CD4+ T cells and activate these cells. Interpretation: Our data suggests the potential involvement of a MOG35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis. Our findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential explanation for the correlation between certain gut microorganisms and MS prevalence. Funding: National Natural Science Foundation of China (82371350 to GY). |
| format | Article |
| id | doaj-art-cf1c75dc35cb45f280b89f0b4117c9ef |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | EBioMedicine |
| spelling | doaj-art-cf1c75dc35cb45f280b89f0b4117c9ef2025-08-20T01:57:24ZengElsevierEBioMedicine2352-39642025-01-0111110551610.1016/j.ebiom.2024.105516Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in contextXin Ma0Jian Zhang1Qianling Jiang2Yong-Xin Li3Guan Yang4Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, ChinaDepartment of Chemistry and the Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, ChinaDepartment of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, ChinaDepartment of Chemistry and the Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China; Corresponding author.Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China; Corresponding author. Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.Summary: Background: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction. Methods: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens. Subsequently, we conducted a range of in vitro and in vivo assays to assess the encephalitogenic potential of these microbial-derived peptides. Findings: We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) shows the ability to activate MOG35-55-specific CD4+ T cells in vitro. Furthermore, P3 shows encephalitogenic capacity and has the potential to induce EAE in some animals. Notably, mice immunized with a combination of P3 and MOG35-55 develop severe EAE. Additionally, dendritic cells could process and present P3 to MOG35-55-specific CD4+ T cells and activate these cells. Interpretation: Our data suggests the potential involvement of a MOG35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis. Our findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential explanation for the correlation between certain gut microorganisms and MS prevalence. Funding: National Natural Science Foundation of China (82371350 to GY).http://www.sciencedirect.com/science/article/pii/S2352396424005528Multiple sclerosisExperimental autoimmune encephalomyelitisMolecular mimicryGut microbiota |
| spellingShingle | Xin Ma Jian Zhang Qianling Jiang Yong-Xin Li Guan Yang Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context EBioMedicine Multiple sclerosis Experimental autoimmune encephalomyelitis Molecular mimicry Gut microbiota |
| title | Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context |
| title_full | Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context |
| title_fullStr | Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context |
| title_full_unstemmed | Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context |
| title_short | Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryResearch in context |
| title_sort | human microbiome derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicryresearch in context |
| topic | Multiple sclerosis Experimental autoimmune encephalomyelitis Molecular mimicry Gut microbiota |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424005528 |
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