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Surface Layer Protein A Expressed in Clostridioides difficile DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein.
Mindur, John E; Yadav, Sudhir K; Ito, Naoko; Senoh, Mitsutoshi; Kato, Haru; Dhib-Jalbut, Suhayl; Ito, Kouichi.
Afiliação
  • Mindur JE; Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  • Yadav SK; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Ito N; Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  • Senoh M; Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  • Kato H; Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo 208-001, Japan.
  • Dhib-Jalbut S; Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo 208-001, Japan.
  • Ito K; Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Microorganisms ; 9(1)2020 Dec 24.
Article em En | MEDLINE | ID: mdl-33374217
ABSTRACT
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 (MBP89-98) 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 Clostridioides difficile, contains an amino acid sequence that activates MBP89-98-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 C. difficile possesses an encephalitogenic mimotope of MBP that activates autoreactive, myelin-specific T cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Microorganisms Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Microorganisms Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos