Department of Bioinformatics, JJT University, Jhunjhunu, Rajasthan, India
Received date: July 30, 2012; Accepted date: October 25, 2012;Published date: November 02, 2012
Citation: Gomase VS, Chitlange NR (2012) Microbial Proteomics Approach for Sensitive Quantitative Predictions of MHC Binding Peptide from Taenia ovis. J Data Mining Genomics Proteomics 3:121. doi: 10.4172/2153-0602.1000121
Copyright: © 2012 Gomase VS, 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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Taenia ovis is a tapeworm parasite with the adult stage of the parasite found in the intestines of dogs, while the intermediate or larval stage is found in the muscles of sheep, causes sheep measles. Peptide fragments of antigen protein can be used to select nonamers for use in rational vaccine design, and to increase the understanding of roles of the immune system in infectious diseases. Analysis shows MHC class II binding peptides of antigen protein from Taenia ovis are important determinants for protection of host from parasitic infection. In this assay, we used PSSM and SVM algorithms for antigen design and predicted the binding affinity of antigen protein having 254 amino acids, which shows 246 nonamers. Binding ability prediction of antigen peptides to Major Histocompatibility Complex (MHC) class I & II molecules is important in vaccine development against sheep measles.
Cysticercosis; Antigen protein; Epitope; PSSM; SVM; MHC; Peptide vaccine
MHC: Major Histocompatibility Complex; PSSMs: Position Specific Scoring Matrices; SVM: Support Vector Machine
Taenia ovis are the smallest nematode parasite of sheep, are responsible for ovine cysticercosis (Sheep Measles), have an unusual life cycle, and are one of the most widespread and clinically important parasites in the world [1,2]. The small adult worms mature in the intestines of an intermediate host, such as a dog [1,2]. Taenia ovis antigen peptides are most suitable for subunit vaccine development, because with single epitope the immune response can be generated in a large population. This approach is based on the phenomenon of cross-protection, whereby infected with a mild strain and is protected against a more severe strain of the same. The phenotype of the resistant transgenic hosts includes fewer centers of initial infection, a delay in symptom development and low accumulation. Antigen protein from Taenia ovis is necessary for new paradigm of synthetic vaccine development and target validation [3-5].
The sheep ingests an egg. The egg hatches in the small intestine and the larval tapeworm burrows through the intestinal wall, and travels to the heart and muscles via the blood. The cysticercus develops in the cardiac and skeletal muscles, reaching the infective stage in about 46 days. When the dog eats the sheep and ingests the cysticercus, the protoscolex attaches to the small intestinal wall and the worm begins to form proglottids, and the lifecycle continues.
In this research work, antigenic epitopes of antigen protein from Taenia ovis is determined using the Kyte and Doolittle , Bull and Breese , Parker et al. , Chothia , Hopp and Woods , Welling et al. , Manavalan and Ponnuswamy , Gomase et al. , hydrophobicity scale and Deleage and Roux, Chou and Fasman, Levitt (parameters) have used to predict the probability that a given sequence of amino acids would form a beta strand in antigenic epitopes [6-14]. 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 log-transformed value related to the IC50 values in nM units. MHC2 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 [15-20]. In addition, we predict those MHC ligands from whose C-terminal end is likely to be the result of proteosomal cleavage [21-25].
Binding of peptides to a number of different alleles using Position Specific Scoring Matrix have been found through this study. An antigen protein sequence is 254 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 MHCI molecules of antigen protein sequence which are as 11mer_H2_Db, 10mer_H2_Db, 9mer_H2_Db, 8mer_H2_Db, and also peptide binders to MHCII molecules of antigen protein sequence as I_Ab.p, I_Ad.p; analysis found antigenic epitopes region in putative antigen protein (Table 1). Additionally, SVM based MHCII-IAb peptide regions were also found; MHCII-IAd peptide regions; MHCII-IAg7 peptide regions and MHCII- RT1.B peptide regions were also found, which represented predicted binders from bacterial antigen protein (Table 2). The predicted binding affinity is normalized by the 1% fractal. Through this study, an improved method for predicting linear epitopes has been described (Table 2). The region of maximal hydrophilicity is likely to be an antigenic site, having hydrophobic characteristics (Figure 1-4), because terminal regions of antigen protein is solvent accessible and unstructured; antibodies against those regions are also likely to recognize the native protein (Figure 5-7). It was shown that an antigen protein is hydrophobic in nature and contains segments of low complexity and high-predicted flexibility (Figure 8-10). Predicted antigenic fragments can bind to MHC molecule, and is the first bottlenecks in vaccine design (Figure 1-4).
|MHC-I||POS.||N||Sequence||C||MW Da)||Score||% OPT.|
Table 1: PSSM based prediction of MHC ligands, from whose C-terminal ends are proteosomal cleavage sites.
|MHC ALLELE||Rank||Sequence||Residue No.||Peptide Score|
Table 2: SVM based prediction of promiscuous MHC class II binding peptides from antigen protein.
An antigen protein from Taenia ovis 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 antigen protein. These predictions of antigen protein, antigenic peptides to MHC class molecules are important in vaccine development from Taenia ovis.