Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Recent studies suggest that migration of Th1 and Th17 cells specific for enteric bacteria from the gut to the CNS may lead to the initiation and/or exacerbation of autoimmune diseases including MS....
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MDPI AG
2020-12-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/1/34 |
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| author | John E. Mindur Sudhir K. Yadav Naoko Ito Mitsutoshi Senoh Haru Kato Suhayl Dhib-Jalbut Kouichi Ito |
| author_facet | John E. Mindur Sudhir K. Yadav Naoko Ito Mitsutoshi Senoh Haru Kato Suhayl Dhib-Jalbut Kouichi Ito |
| author_sort | John E. Mindur |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Recent studies suggest that migration of Th1 and Th17 cells specific for enteric bacteria from the gut to the CNS may lead to the initiation and/or exacerbation of autoimmune diseases including MS. Human leukocyte antigen (HLA)-DR15 is an MHC class II (MHCII) haplotype highly associated with the development of MS that contains the two HLA-DRB* genes, DRB1*1501 (DR2b) and DRB5*0101 (DR2a). To identify enteric bacteria which harbor antigenic epitopes that activate myelin-specific T cells and drive CNS inflammation, we screened for enteric bacteria which express cross-reactive epitopes (‘mimotopes’) of an immunodominant myelin basic protein 89–98 (MBP<sub>89-98</sub>) epitope. Based on known MHCII HLA-DR2a amino acid binding motifs and cultivation with splenic T cells isolated from MBP-T cell receptor (TCR)/DR2a transgenic (Tg) mice, we discovered that a certain variant of surface layer protein A (SLPA), which is expressed by a subtype of <i>Clostridioides difficile</i>, contains an amino acid sequence that activates MBP<sub>89-98</sub>-reactive T cells. Furthermore, activation of MBP-specific T cells by SLPA upon active immunization induced experimental autoimmune encephalomyelitis (EAE) in MBP-TCR/DR2a Tg mice. This study suggests that a unique strain of <i>C. difficile</i> possesses an encephalitogenic mimotope of MBP that activates autoreactive, myelin-specific T cells. |
| first_indexed | 2024-03-10T13:48:05Z |
| format | Article |
| id | doaj.art-1119c2a3e49b431fbc214c000017587d |
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| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T13:48:05Z |
| publishDate | 2020-12-01 |
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| series | Microorganisms |
| spelling | doaj.art-1119c2a3e49b431fbc214c000017587d2023-11-21T02:23:12ZengMDPI AGMicroorganisms2076-26072020-12-01913410.3390/microorganisms9010034Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic ProteinJohn E. Mindur0Sudhir K. Yadav1Naoko Ito2Mitsutoshi Senoh3Haru Kato4Suhayl Dhib-Jalbut5Kouichi Ito6Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USADepartment of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USADepartment of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USADepartment of Bacteriology II, National Institute of Infectious Diseases, Tokyo 208-001, JapanDepartment of Bacteriology II, National Institute of Infectious Diseases, Tokyo 208-001, JapanDepartment of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USADepartment of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USAMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Recent studies suggest that migration of Th1 and Th17 cells specific for enteric bacteria from the gut to the CNS may lead to the initiation and/or exacerbation of autoimmune diseases including MS. Human leukocyte antigen (HLA)-DR15 is an MHC class II (MHCII) haplotype highly associated with the development of MS that contains the two HLA-DRB* genes, DRB1*1501 (DR2b) and DRB5*0101 (DR2a). To identify enteric bacteria which harbor antigenic epitopes that activate myelin-specific T cells and drive CNS inflammation, we screened for enteric bacteria which express cross-reactive epitopes (‘mimotopes’) of an immunodominant myelin basic protein 89–98 (MBP<sub>89-98</sub>) epitope. Based on known MHCII HLA-DR2a amino acid binding motifs and cultivation with splenic T cells isolated from MBP-T cell receptor (TCR)/DR2a transgenic (Tg) mice, we discovered that a certain variant of surface layer protein A (SLPA), which is expressed by a subtype of <i>Clostridioides difficile</i>, contains an amino acid sequence that activates MBP<sub>89-98</sub>-reactive T cells. Furthermore, activation of MBP-specific T cells by SLPA upon active immunization induced experimental autoimmune encephalomyelitis (EAE) in MBP-TCR/DR2a Tg mice. This study suggests that a unique strain of <i>C. difficile</i> possesses an encephalitogenic mimotope of MBP that activates autoreactive, myelin-specific T cells.https://www.mdpi.com/2076-2607/9/1/34<i>Clostridioides difficile</i>surface layer protein Amultiple sclerosismyelin basic proteinmimotope |
| spellingShingle | John E. Mindur Sudhir K. Yadav Naoko Ito Mitsutoshi Senoh Haru Kato Suhayl Dhib-Jalbut Kouichi Ito Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein Microorganisms <i>Clostridioides difficile</i> surface layer protein A multiple sclerosis myelin basic protein mimotope |
| title | Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein |
| title_full | Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein |
| title_fullStr | Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein |
| title_full_unstemmed | Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein |
| title_short | Surface Layer Protein A Expressed in <i>Clostridioides difficile</i> DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein |
| title_sort | surface layer protein a expressed in i clostridioides difficile i djns06 36 possesses an encephalitogenic mimotope of myelin basic protein |
| topic | <i>Clostridioides difficile</i> surface layer protein A multiple sclerosis myelin basic protein mimotope |
| url | https://www.mdpi.com/2076-2607/9/1/34 |
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