scholarly journals Surface Layer Protein A Expressed in Clostridioides difficile DJNS06-36 Possesses an Encephalitogenic Mimotope of Myelin Basic Protein

2020 ◽  
Vol 9 (1) ◽  
pp. 34
Author(s):  
John E. Mindur ◽  
Sudhir K. Yadav ◽  
Naoko Ito ◽  
Mitsutoshi Senoh ◽  
Haru Kato ◽  
...  
Keyword(s):  
T Cells ◽  
Surface Layer ◽  
Amino Acid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Demyelinating Disease ◽  
Protein A ◽  
Enteric Bacteria ◽  
Surface Layer Protein ◽  
Clostridioides Difficile

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.

scholarly journals Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells

2004 ◽  
Vol 101 (32) ◽  
pp. 11749-11754 ◽  
Author(s):  
Z. Illes ◽  
J. N. H. Stern ◽  
J. Reddy ◽  
H. Waldner ◽  
M. P. Mycko ◽  
...  
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Humanized Mice

scholarly journals Tolerance Induction and Autoimmune Encephalomyelitis Amelioration After Administration of Myelin Basic Protein–derived Peptide

1997 ◽  
Vol 186 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Suzana Marusic ◽  
Susumu Tonegawa
Keyword(s):  
T Cells ◽  
Myelin Basic Protein ◽  
Intraperitoneal Injection ◽  
Basic Protein ◽  
Demyelinating Disease ◽  
Critical Role ◽  
Tolerance Induction ◽  
Autoimmune Encephalomyelitis ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is an animal model of paralyzing human disease, multiple sclerosis. EAE is readily induced by immunization with myelin basic protein (MBP) in mice transgenic for an αβ T cell receptor (TCR) that is specific for MBP. Subcutaneous injection of p17 (a peptide consisting of 17 NH2-terminal aminoacids of MBP) in complete Freund's adjuvant (CFA) causes paralysis. Induction of paralysis is inhibited by prior intraperitoneal injection of the same peptide in incomplete Freund's adjuvant (IFA). In addition, ongoing paralysis is ameliorated by subsequent intraperitoneal injection of p17 in IFA. Tolerance induction is equally efficient in Fas-deficient and IL-4–deficient TCR-transgenic mice, suggesting that neither activation-induced cell death nor differentiation into Th2 type cells plays a role in the tolerance induction. Tolerance induction by p17 seems to be based on reduction in the responsiveness of anti-MBP T cells, as documented by lower overall antigen-induced lymphokine production and proliferation, as well as diminished upregulation of early activation marker CD69 by tolerized T cells. We propose that continuous encounters of MBP-specific T cells with p17 play a critical role in the induction and maintenance of tolerance.

scholarly journals Proteolytic and peroxidatic reactions of commercial horseradish peroxidase with myelin basic protein

1978 ◽  
Vol 169 (3) ◽  
pp. 567-575 ◽  
Author(s):  
Wendy Cammer ◽  
Lesley Z. Bieler ◽  
William T. Norton
Keyword(s):  
Horseradish Peroxidase ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Protein A ◽  
Low Molecular Weight ◽  
Basic Proteins ◽  
Molecular Weights ◽  
Low Concentrations ◽  
High Concentrations ◽  
A Minor

Degradation of myelin basic protein during incubations with high concentrations of horseradish peroxidase has been demonstrated [Johnson & Cammer (1977) J. Histochem. Cytochem.25, 329–336]. Possible mechanisms for the interaction of the basic protein with peroxidase were investigated in the present study. Because the peroxidase samples previously observed to degrade basic protein were mixtures of isoenzymes, commercial preparations of the separated isoenzymes were tested, and all three degraded basic protein, but to various extents. Three other basic proteins, P2 protein from peripheral nerve myelin, lysozyme and cytochrome c, were not degraded by horseradish peroxidase under the same conditions. Inhibitor studies suggested a minor peroxidatic component in the reaction. Therefore the peroxidatic reaction with basic protein was studied by using low concentrations of peroxidase along with H2O2. Horseradish peroxidase plus H2O2 caused the destruction of basic protein, a reaction inhibited by cyanide, azide, ferrocyanide, tyrosine, di-iodotyrosine and catalase. Lactoperoxidase plus H2O2 and myoglobin plus H2O2 were also effective in destroying the myelin basic protein. Low concentrations of horseradish peroxidase plus H2O2 were not active against other basic proteins, but did destroy casein and fibrinogen. Although high concentrations of peroxidase alone degraded basic protein to low-molecular-weight products, suggesting the operation of a proteolytic enzyme contaminant in the absence of H2O2, incubations with catalytic concentrations of peroxidase in the presence of H2O2 converted basic protein into products with high molecular weights. Our data suggest a mechanism for the latter, peroxidatic, reaction where polymers would form by linking the tyrosine side chains in basic-protein molecules. These data show that the myelin basic protein is unusually susceptible to peroxidatic reactions.

Shark Myelin Basic Protein: Amino Acid Sequence, Secondary Structure, and Self-Association

1990 ◽  
Vol 55 (3) ◽  
pp. 950-955 ◽  
Author(s):  
Trudy J. Milne ◽  
Annette R. Atkins ◽  
Juanita A. Warren ◽  
Wendy P. Auton ◽  
Ross Smith
Keyword(s):  
Amino Acid ◽  
Secondary Structure ◽  
Amino Acid Sequence ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Protein Amino Acid ◽  
Protein Amino Acid Sequence ◽  
Self Association

scholarly journals A Computational Approach for Protein-Protein Interactions of Bacterial Surface Layer Protein with Human Erb3 and αIIB-β3 Receptors

2021 ◽  
Vol 12 (1) ◽  
pp. 420-430
Keyword(s):  
Surface Layer ◽  
Molecular Docking ◽  
Protein Interactions ◽  
Protein A ◽  
Computational Approach ◽  
Microbial Interactions ◽  
Protein Protein Interactions ◽  
Epithelial Surface ◽  
Surface Receptors ◽  
Surface Layer Protein

Host microbial interactions had significant factors in maintains homeostasis and immune-related activity. One such interaction made by Lactobacillus sp. with Surface layer proteins (Slps) had been studied through a computational approach. Erb3 and αIIB-β3, which are epithelial surface layer receptors, are subjected to interact with the Slp homology model. Both cell surface receptors were subjected to interact through computational docking, followed by molecular dynamics simulations through the coarse-grain method to explore the conformational stability. Through the implementation of the molecular docking for the surface layer protein A, we have shown the surface layer protein A, protein-protein interactions are higher in cellular receptors with epidermal growth factor receptor at an -34.45 ΔG and -51.19 ΔG through molecular docking with Erb3 and αIIB-β3. This study shows the unique interaction of Slp with the epithelial surface receptors like Erb3 and αIIB-β3, which are multipurpose applications in microbial-based drug therapeutics.

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