PMID- 33374217
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210126
IS  - 2076-2607 (Print)
IS  - 2076-2607 (Electronic)
IS  - 2076-2607 (Linking)
VI  - 9
IP  - 1
DP  - 2020 Dec 24
TI  - Surface Layer Protein A Expressed in Clostridioides difficile DJNS06-36 Possesses 
      an Encephalitogenic Mimotope of Myelin Basic Protein.
LID - 10.3390/microorganisms9010034 [doi]
LID - 34
AB  - 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(89-98)) 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 MBP(89-98)-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.
FAU - Mindur, John E
AU  - Mindur JE
AD  - Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, 
      NJ 08854, USA.
AD  - Center for Systems Biology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA 02114, USA.
FAU - Yadav, Sudhir K
AU  - Yadav SK
AD  - Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, 
      NJ 08854, USA.
FAU - Ito, Naoko
AU  - Ito N
AD  - Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, 
      NJ 08854, USA.
FAU - Senoh, Mitsutoshi
AU  - Senoh M
AD  - Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo 
      208-001, Japan.
FAU - Kato, Haru
AU  - Kato H
AD  - Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo 
      208-001, Japan.
FAU - Dhib-Jalbut, Suhayl
AU  - Dhib-Jalbut S
AD  - Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, 
      NJ 08854, USA.
FAU - Ito, Kouichi
AU  - Ito K
AD  - Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, 
      NJ 08854, USA.
LA  - eng
GR  - NJHF-PC 90-12/New Jersey Health Foundation/
PT  - Journal Article
DEP - 20201224
PL  - Switzerland
TA  - Microorganisms
JT  - Microorganisms
JID - 101625893
PMC - PMC7824458
OTO - NOTNLM
OT  - Clostridioides difficile
OT  - mimotope
OT  - multiple sclerosis
OT  - myelin basic protein
OT  - surface layer protein A
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/31 06:00
MHDA- 2020/12/31 06:01
PMCR- 2020/12/24
CRDT- 2020/12/30 01:00
PHST- 2020/11/26 00:00 [received]
PHST- 2020/12/14 00:00 [revised]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2020/12/30 01:00 [entrez]
PHST- 2020/12/31 06:00 [pubmed]
PHST- 2020/12/31 06:01 [medline]
PHST- 2020/12/24 00:00 [pmc-release]
AID - microorganisms9010034 [pii]
AID - microorganisms-09-00034 [pii]
AID - 10.3390/microorganisms9010034 [doi]
PST - epublish
SO  - Microorganisms. 2020 Dec 24;9(1):34. doi: 10.3390/microorganisms9010034.