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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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.
Schistosomiasis; Immunoproteomics; Thioredoxin glutathione reductase PSSM; SVM
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 . 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 . Because of this, the search for a new drug against Schistosomiasis is a necessity and a priority according to the World Health Organization .
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 .
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.
|RANK||POS.||N||SEQUENCE||C||MW (Da)||SCORE||% OPT.|
Table 1: PSSM based prediction of MHC ligands, from whose C-terminal end are proteosomal cleavage sites.
|MHC ALLELE||Rank||Sequence||Residue No.||Peptide|
Table 2: SVM based prediction of promiscuous MHC class II binding peptides from antigen Protein.
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.