Perspectives on the Prediction of the PLP's Epitopes Involved in Multiple Sclerosis

Overview

Journal Iran J Biotechnol

Specialty Biotechnology

Date 2017 Sep 30

PMID 28959348

Citations 2

Authors

Zahra Zamanzadeh

Mitra Ataei

Seyed Massood Nabavi

Ghasem Ahangari

Mehdi Sadeghi

Mohammad Hosein Sanati

Affiliations

Soon will be listed here.

Abstract

Background: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade.

Objectives: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis.

Materials And Methods: As there wasn't any tertiary structure of PLP available in the Protein Data Bank (PDB) and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective , was performed to fi nd PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens (HLA). The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms.

Results: Three common regions, AA, AA, and AA were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA in bacteria showed a similar peptide in bacteria (mainly consistent with that of clostridium and mycobacterium) and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS.

Conclusions: Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally (). In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost.

Citing Articles

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens.

Franca L, Fontes-Dantas F, Garcia D, de Araujo A, da Costa Goncalves J, Rego C Arq Neuropsiquiatr. 2023; 81(4):357-368.

PMID: 37160141 PMC: 10169219. DOI: 10.1055/s-0043-1768698.

Cytokine and Chemokine Concentrations as Biomarkers of Feline Mycobacteriosis.

OHalloran C, McCulloch L, Rentoul L, Alexander J, Hope J, Gunn-Moore D Sci Rep. 2018; 8(1):17314.

PMID: 30470763 PMC: 6251861. DOI: 10.1038/s41598-018-35571-5.

References

Tuohy V, Lu Z, Sobel R, Laursen R, LEES M . Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice. J Immunol. 1989; 142(5):1523-7. View

Pereira G, Meng F, Kockara N, Yang B, Wight P . Targeted deletion of the antisilencer/enhancer (ASE) element from intron 1 of the myelin proteolipid protein gene (Plp1) in mouse reveals that the element is dispensable for Plp1 expression in brain during development and remyelination. J Neurochem. 2012; 124(4):454-65. PMC: 3557533. DOI: 10.1111/jnc.12092. View

Tsunoda I, Fujinami R . Neuropathogenesis of Theiler's murine encephalomyelitis virus infection, an animal model for multiple sclerosis. J Neuroimmune Pharmacol. 2009; 5(3):355-69. PMC: 2888670. DOI: 10.1007/s11481-009-9179-x. View

Popot J, Pham Dinh D, Dautigny A . Major Myelin proteolipid: the 4-alpha-helix topology. J Membr Biol. 1991; 120(3):233-46. DOI: 10.1007/BF01868534. View

Schwimmbeck P, Dyrberg T, Drachman D, Oldstone M . Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus. J Clin Invest. 1989; 84(4):1174-80. PMC: 329775. DOI: 10.1172/JCI114282. View

Lovell S, Davis I, Arendall 3rd W, de Bakker P, Word J, Prisant M . Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins. 2003; 50(3):437-50. DOI: 10.1002/prot.10286. View

WHITHAM R, Jones R, Hashim G, Hoy C, Wang R, Vandenbark A . Location of a new encephalitogenic epitope (residues 43 to 64) in proteolipid protein that induces relapsing experimental autoimmune encephalomyelitis in PL/J and (SJL x PL)F1 mice. J Immunol. 1991; 147(11):3803-8. View

Poole B, Scofield R, Harley J, James J . Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus. Autoimmunity. 2006; 39(1):63-70. DOI: 10.1080/08916930500484849. View

Greer J, Kuchroo V, Sobel R, LEES M . Identification and characterization of a second encephalitogenic determinant of myelin proteolipid protein (residues 178-191) for SJL mice. J Immunol. 1992; 149(3):783-8. View

10.

Schloot N, Willemen S, Duinkerken G, Drijfhout J, de Vries R, Roep B . Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to Coxsackie or proinsulin peptides do not crossreact with homologous counterpart. Hum Immunol. 2001; 62(4):299-309. DOI: 10.1016/s0198-8859(01)00223-3. View

11.

Tuohy V, Thomas D . Sequence 104-117 of myelin proteolipid protein is a cryptic encephalitogenic T cell determinant for SJL/J mice. J Neuroimmunol. 1995; 56(2):161-70. DOI: 10.1016/0165-5728(94)00143-c. View

12.

Goldenberg M . Pharmaceutical approval update. P T. 2010; 34(10):569-74. PMC: 2799142. View

13.

Grau-Lopez L, Raich D, Ramo-Tello C, Naranjo-Gomez M, Davalos A, Pujol-Borrell R . Myelin peptides in multiple sclerosis. Autoimmun Rev. 2009; 8(8):650-3. DOI: 10.1016/j.autrev.2009.02.013. View

14.

McMahon R, Friis L, Siebold C, Friese M, Fugger L, Jones E . Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 5):447-54. PMC: 3087623. DOI: 10.1107/S0907444911007888. View

15.

Greer J, Sobel R, Sette A, Southwood S, LEES M, Kuchroo V . Immunogenic and encephalitogenic epitope clusters of myelin proteolipid protein. J Immunol. 1996; 156(1):371-9. View

16.

Kondo T, Yamamura T, Inobe J, Ohashi T, Takahashi K, Tabira T . TCR repertoire to proteolipid protein (PLP) in multiple sclerosis (MS): homologies between PLP-specific T cells and MS-associated T cells in TCR junctional sequences. Int Immunol. 1996; 8(1):123-30. DOI: 10.1093/intimm/8.1.123. View

17.

Fletcher J, Lalor S, Sweeney C, Tubridy N, Mills K . T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010; 162(1):1-11. PMC: 2990924. DOI: 10.1111/j.1365-2249.2010.04143.x. View

18.

Wu X, Shang B, Yang R, Yu H, Ma Z, Shen X . The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells. Cell Res. 2004; 14(5):400-6. PMC: 7091875. DOI: 10.1038/sj.cr.7290240. View

19.

McKay K, Kwan V, Duggan T, Tremlett H . Risk factors associated with the onset of relapsing-remitting and primary progressive multiple sclerosis: a systematic review. Biomed Res Int. 2015; 2015:817238. PMC: 4329850. DOI: 10.1155/2015/817238. View

20.

Greene M, Ercolini A, DeGutes M, Miller S . Differential induction of experimental autoimmune encephalomyelitis by myelin basic protein molecular mimics in mice humanized for HLA-DR2 and an MBP(85-99)-specific T cell receptor. J Autoimmun. 2008; 31(4):399-407. PMC: 2640492. DOI: 10.1016/j.jaut.2008.09.004. View