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ISSN: 2153-0769
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Immunoproteomics Approach for Development of Synthetic Peptide Vaccine from Thioredoxin Glutathione Reductase

Somnath Waghmare1*,Virendra Gomase2, Jaywant Dhole2 and Ramrao Chavan2

1Department of Zoology, Nowrosjee Wadia College of Arts and Science, Pune-1, India

2Department of Zoology, Dr. Babasaheb Ambedkar Marathawada University, Aurangabad, India

*Corresponding Author:
Dr. Somnath Waghmare
Assistant Professor, Department of Zoology Nowrosjee
Wadia College of Arts and Science, Pune-1, India
E-mail: [email protected]

Received date: April 16, 2012; Accepted date: April 25, 2012; Published date: April 27, 2012

Citation: Waghmare S, Dhole J, Chavan R (2012) Immunoproteomics Approach for Development of Synthetic Peptide Vaccine from Thioredoxin Glutathione Reductase. Metabolomics 2:111. doi:10.4172/2153-0769.1000111

Copyright: © 2012 Waghmare S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Schistosomiasis is the second most widespread human parasitic disease. It is principally treated with one drug, praziquantel, which is administered to 100 million people each year; less sensitive strains of schistosomes are emerging. One of the most appealing drug targets against schistosomiasis is thioredoxin glutathione reductase (TGR). This natural chimeric enzyme is a peculiar fusion of a glutaredoxin domain with a thioredoxin selenocysteine (U)-containing reductase domain. Selenocysteine is located on a flexible C-terminal arm that is usually disordered in the available structures of the protein and is essential for the full catalytic activity of TGR. MHC molecules are cell surface proteins, which take active part in host immune reactions and involvement of MHC class in response to almost all antigens and it give effects on specific sites. Predicted MHC binding regions acts like red flags for antigen specific and generate immune response against the parent antigen. So a small fragment of antigen can induce immune response against whole antigen. This theme is implemented in designing subunit and synthetic peptide vaccines. In this study,
we analyzed thioredoxin glutathione reductase of Schistosoma mansoni and is allows potential drug targets to identify active sites, which form antibodies against or infection. The method integrates prediction of peptide MHC class binding; proteosomal C terminal cleavage and TAP transport efficiency. Antigenic epitopes of thioredoxin glutathione reductase are important antigenic determinants against the various toxic reactions and infections.

Keywords

Schistosomiasis; Immunoproteomics; Thioredoxin glutathione reductase PSSM; SVM

Introduction

Schistosomes are human platyhelminth parasites causing Schistosomiasis, a severe disease still classified among the major causes of mortality in tropical and subtropical countries, affecting more than 200 million people [1]. The only drug employed to fight the disease is praziquantel, whose efficacy is restricted to the adult stages of the parasite and whose mechanism of action is still incompletely clarified [2,3]. Because this drug is administered to 100 million people every year, some less sensitive strains have already been isolated, and given the massive drug administration, resistance might become a serious problem [3]. Because of this, the search for a new drug against Schistosomiasis is a necessity and a priority according to the World Health Organization [4].

Methodology

In this research work antigenic epitopes of antigen protein from thioredoxin glutathione reductase of Schistosoma mansoni is determined using the Gomase, Hopp and Woods, Welling, Parker and Wolfenden, antigenicity [5-8]. The major histocompatibility complex (MHC) peptide binding of antigen protein is predicted using neural networks trained on C terminals of known epitopes. In analysis predicted MHC/peptide binding of antigen protein is a logtransformed value related to the IC50 values in nM units. RANKPEP predicts peptide binders to MHCI and MHCII molecules from protein sequences or sequence alignments using Position Specific Scoring Matrices (PSSMs). Support Vector Machine (SVM) based method for prediction of promiscuous MHC class II binding peptides. SVM has been trained on the binary input of single amino acid sequence [9-14]. In addition, we predict those MHC ligands from whose C-terminal end is likely to be the result of proteosomal cleavage [15].

Results and Interpretation

We found binding of peptides to a number of different alleles using Position Specific Scoring Matrix. A thioredoxin glutathione reductase antigen protein sequence is 598 residues long, having antigenic MHC binding peptides. MHC molecules are cell surface glycoproteins, which take active part in host immune reactions and involvement of MHC class-I and MHC II in response to almost all antigens. PSSM based server predict the peptide binders to MHC I molecules of thioredoxin glutathione reductase to MHCII molecules of thioredoxin glutathione reductase sequence as H2_Db, I_Ab, I_Ag7, I_Ad, analysis found antigenic epitopes region in thioredoxin glutathione reductase (Table 1 and 2). We also found the SVM based MHCII-IAb; MHCII-IAd; MHCII-IAg7 and MHCII- RT1.B peptide regions, which represented predicted binders from thioredoxin glutathione reductase. The predicted binding affinity is normalized by the 1% fractil. We describe an improved method for predicting linear epitopes (Table 2). The region of maximal hydrophilicity is likely to be an antigenic site, having hydrophobic characteristics, because terminal regions of thioredoxin glutathione reductase is solvent accessible and unstructured, antibodies against those regions are also likely to recognize the native protein (Figures 1-4). It was shown that thioredoxin glutathione reductase is hydrophobic in nature and contains segments of low complexity and high-predicted flexibility. Predicted antigenic fragments can bind to MHC molecule is the first bottlenecks in vaccine design.

metabolomics-Antigenicity-plot

Figure 1: Antigenicity plot of antigen protein by Welling, et al. scale.

metabolomics-antigen-protein

Figure 2: Antigenicity plot of antigen protein by HPLC / Parker, et al. scale.

metabolomics-Hydrophobicity-plot

Figure 3: Hydrophobicity plot of antigen protein by Wolfenden, et al. scale.

metabolomics-Hydrophobicity-plot

Figure 4: Hydrophobicity plot of antigen protein by Hopp & Woods scale.

RANK POS. N SEQUENCE C MW (Da) SCORE % OPT.
8mer_H2_Db 439 AGK PQLTPVAI QAG 820.0 15.001 28.58 %
8mer_H2_Db 24 ILF SKTTCPYC KKV 884.03 14.29 27.22 %
8mer_H2_Db 224 VTY LNAKGRLI SPH 866.07 13.696 26.09 %
8mer_H2_Db 8 DGT SQWLRKTV DSA 976.17 13.263 25.27 %
8mer_H2_Db 246 QKV STITGNKI ILA 814.92 11.607 22.11 %
8mer_H2_Db 75 VPQ MFVRGKFI GDS 979.25 11.583 22.07 %
8mer_H2_Db 241 ITD KNQKVSTI TGN 899.04 11.41 21.74 %
8mer_H2_Db 283 FSL PYFPGKTL VIG 904.08 11.377 21.67 %
8mer_H2_Db 52 ELD QLSNGSAI QKC 770.84 11.253 21.44 %
8mer_H2_Db 398 PQL SKVLCETV GVK 860.03 9.948 18.95 %
9mer_H2_Db 189 DRS KISHNWSTM VEG 1062.23 25.291 50.22 %
9mer_H2_Db 152 GLG GTCVNVGCI PKK 847.0 16.502 32.76 %
9mer_H2_Db 527 LVC RKSDNMRVL GLH 1100.3 13.709 27.22 %
9mer_H2_Db 539 GLH VLGPNAGEI TQG 850.97 12.87 25.55 %
9mer_H2_Db 500 DIE VYHSNFKPL EWT 1086.26 11.747 23.32 %
9mer_H2_Db 328 DQQ MAEKVGDYM ENH 1025.2 11.231 22.30 %
9mer_H2_Db 524 YMK LVCRKSDNM RVL 1047.25 10.643 21.13 %
9mer_H2_Db 514 TVA HREDNVCYM KLV 1148.28 10.591 21.03 %
9mer_H2_Db 444 LTP VAIQAGRYL ARR 972.16 10.381 20.61 %
9mer_H2_Db 272 AVE YGITSDDLF SLP 1012.09 9.69 19.24 %
10mer_H2_Db 464 TEL TDYSNVATTV FTP 1052.09 23.99 40.76 %
10mer_H2_Db 503 VYH SNFKPLEWTV AHR 1179.37 19.929 33.86 %
10mer_H2_Db 98 DEL AGIVNESKYD YDL 1077.16 15.442 26.24 %
10mer_H2_Db 568 DRT IGIHPTCSET FTT 1039.17 14.934 25.37 %
10mer_H2_Db 215 YKV ALRDNQVTYL NAK 1174.32 14.69 24.96 %
10mer_H2_Db 587 TKK SGVSPIVSGC UG 887.02 13.676 23.24 %
10mer_H2_Db 257 ILA TGERPKYPEI PGA 1171.33 13.328 22.64 %
10mer_H2_Db 423 DEQ TTVSNVYAIG DIN 1006.11 12.481 21.21 %
11mer_H2_Db 338 YME NHGVKFAKLCV PDE 1197.45 21.22 26.69 %
11mer_H2_Db 98 DEL AGIVNESKYDY DLI 1240.34 20.391 25.65 %
11mer_H2_Db 527 LVC RKSDNMRVLGL HVL 1270.51 13.574 17.08 %
11mer_H2_Db 205 QSH IGSLNWGYKVA LRD 1166.37 13.026 16.39 %
11mer_H2_Db 423 DEQ TTVSNVYAIGD INA 1121.2 12.765 16.06 %
11mer_H2_Db 474 TTV FTPLEYGACGL SEE 1152.34 11.753 14.78 %
11mer_H2_Db 358 LKV VDTENNKPGLL LVK 1181.3 10.68 13.43 %

Table 1: PSSM based prediction of MHC ligands, from whose C-terminal end are proteosomal cleavage sites.

MHC  ALLELE Rank Sequence Residue No. Peptide
I-Ab 1 VATTVFTPL 518 1.126
I-Ab 2 RYLARRLFA 499 1.023
I-Ab 3 PTCSETFTT 621 0.996
I-Ab 4 SLPYFPGKT 330 0.991
I-Ad 1 QAGLLSHAL 216 0.924
I-Ad 2 GGSGGLAAG 164 0.765
I-Ad 3 GASYVALEC 342 0.724
I-Ad 4 GACGLSEED 529 0.709
I-Ag7 1 GIGAAKAFT 1 1.920
I-Ag7 2 GKEAAKYGA 172 1.916
I-Ag7 3 GGLAAGKEA 167 1.740
I-Ag7 4 VIFAVGREP 436 1.739
RT1.B 1 TTVFTPLEY 520 1.117
RT1.B 2 ETFTTLHVT 625 1.028
RT1.B 3 ATKADFDRT 608 0.927
RT1.B 4 TCSETFTTL 622 0.834

Table 2: SVM based prediction of promiscuous MHC class II binding peptides from antigen Protein.

Conclusion

Thioredoxin glutathione reductase of Schistosoma mansoni peptide nonamers are from a set of aligned peptides known to bind to a given MHC molecule as the predictor of MHC peptide binding. MHCII molecules bind peptides in similar yet different modes and alignments of MHCII ligands were obtained to be consistent with the binding mode of the peptides to their MHC class, this means the increase in affinity of MHC binding peptides may result in enhancement of immunogenicity of thioredoxin glutathione reductase. These predicted of thioredoxin glutathione reductase antigenic peptides to MHC class molecules are important in vaccine development from Schistosoma mansoni.

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