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Research Article - (2012) Volume 3, Issue 1

Sensitive Quantitative Predictions of MHC Binding Peptides and Fragment Based Peptide Vaccines from Taenia crassiceps

Gomase VS* and Chitlange NR
Department of Bioinformatics, JJT University, Jhunjhunu Rajasthan, 333001, India
*Corresponding Author: Gomase VS, Department of Bioinformatics, JJT University, Jhunjhunu Rajasthan, 333001, India Email:

Abstract

Taenia crassiceps is a member of the Taenia genus. It is a tapeworm. It is related to Taenia solium, the pork tapeworm, and to Taenia saginata, the beef tapeworm. Its larvae eat tiny holes in the human retina, eventually detaching it. The life cycle is when an adult lays eggs inside a wild canine. 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 crassiceps are important determinant for protection of host form parasitic infection. In this assay, we used PSSM and SVM algorithms for antigen design and predicted the binding affinity of antigen protein having 72 amino acids, which shows 64 nonamers. Binding ability prediction of antigen peptides to major histocompatibility complex (MHC) class I & II molecules is important in vaccine development from Taenia crassiceps.

Keywords: Antigen protein; Epitope; PSSM; SVM; MHC; Peptide vaccine

Abbreviations

GES: Goldman; Engelberg and Steitz; MHC: Major Histocompatibility Complex; PSSMs: Position Specific Scoring Matrices; SVM: Support Vector Machine

Introduction

Trichinella species are the smallest nematode parasite of humans; have an unusual life cycle and are one of the most widespread and clinically important parasites in the world [1]. The small adult worms mature in the intestines of an intermediate host such as a pig [1,2]. Taenia crassiceps antigen peptides are most suitable for subunit vaccine development because with single epitope; the immune response can be generated in 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 crassiceps is necessary for new paradigm of synthetic vaccine development and target validation [3-5].

Methodology

In this research work antigenic epitopes of antigen protein from Taenia crassiceps is determined using the Gomase in 2007; Welling; Eisenberg; Parker and Chou & Fasman and Levitt antigenicity [6- 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 log-transformed value related to the IC50 values in nM units. MHC2Pred 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 [15-18].

Results and Interpretations

We found binding of peptides to a number of different alleles using Position Specific Scoring Matrix. An antigen protein sequence is 44 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 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). We also found the SVM based MHCII-IAb peptide regions; MHCII-IAd peptide regions; MHCII-IAg7 peptide regions and MHCII- RT1.B peptide regions; which represented predicted binders from bacterial antigen protein (Table 2). 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 a terminal region of antigen protein is solvent accessible and unstructured; antibodies against those regions are also likely to recognize the native protein (Figure 1, 2 and 3). It was shown that an antigen protein is hydrophobic in nature and contains segments of low complexity and high-predicted flexibility (Figure 4 and 5). Predicted antigenic fragments can bind to MHC molecule is the first bottlenecks in vaccine design.

MHC-I POS. N Sequence C MW (Da) Score % OPT.
8mer_H2_Db 220 LNE LEEDFRTI LSI 1004.12 16.314 31.08 %
8mer_H2_Db 95 RQV AQYNNFSI FSK 938.01 13.407 25.54 %
8mer_H2_Db 44 ICQ FNLRCLEF LKS 1023.23 9.894 18.85 %
8mer_H2_Db 38 KAV PSLICQFN LRC 903.07 9.7 18.48 %
8mer_H2_Db 139 DHL PINPEVKI SNG 891.08 8.916 16.98 %
8mer_H2_Db 322 PVS RKAGPMTY QML 905.08 8.704 16.58 %
8mer_H2_Db 96 QVA QYNNFSIF SKK 1014.11 8.63 16.44 %
9mer_H2_Db 63 EMY FMLCLIDHI ISN 1086.38 20.064 39.84 %
9mer_H2_Db 95 RQV AQYNNFSIF SKK 1085.19 19.926 39.56 %
9mer_H2_Db 130 MEL FAHWSKDHL PIN 1099.25 19.277 38.27 %
9mer_H2_Db 44 ICQ FNLRCLEFL KSY 1136.39 15.072 29.93 %
9mer_H2_Db 41 PSL ICQFNLRCL EFL 1091.36 13.216 26.24 %
9mer_H2_Db 38 KAV PSLICQFNL RCL 1016.23 11.437 22.71 %
9mer_H2_Db 184 GYD QLIKNAREL YTE 1066.27 11.399 22.63 %
10mer_H2_Db 306 VSP SILKPLADYG ILN 1058.25 22.969 39.02 %
10mer_H2_Db 94 FRQ VAQYNNFSIF SKK 1184.32 19.021 32.32 %
10mer_H2_Db 73 HII SNYEPFRKGF ATK 1226.37 16.158 27.45 %
10mer_H2_Db 95 RQV AQYNNFSIFS KKN 1172.27 16.055 27.28 %
10mer_H2_Db 206 SIF NGEINEKEKA ELN 1113.19 15.416 26.19 %
10mer_H2_Db 9 LVK SAIDNEEVNP SLH 1069.1 11.88 20.18 %
10mer_H2_Db 70 LID HIISNYEPFR KGF 1257.43 11.82 20.08 %
11mer_H2_Db 94 FRQ VAQYNNFSIFS KKN 1271.4 13.696 17.23 %
11mer_H2_Db 285 DYS KTETNYESYPV QRE 1312.4 10.441 13.13 %
11mer_H2_Db 322 PVS RKAGPMTYQML EDD 1277.56 9.568 12.04 %
11mer_H2_Db 57 SYI SRKEMYFMLCL IDH 1402.76 9.078 11.42 %
11mer_H2_Db 39 AVP SLICQFNLRCL EFL 1291.6 7.777 9.78 %
11mer_H2_Db 8 ELV KSAIDNEEVNP SLH 1197.27 6.901 8.68 %
11mer_H2_Db 58 YIS RKEMYFMLCLI DHI 1428.84 6.462 8.13 %

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

MHC
ALLELE
Rank Sequence Residue
No.
Peptide
Score
I-Ab 1 PSIKDLQRE 39 0.967
I-Ab 2 NTLTNDKRV 61 0.815
I-Ab 3 LTLGVNTLT 56 0.560
I-Ab 4 MLLTLGVNT 54 0.534
I-Ad 1 LSAMLLTLG 51 0.726
I-Ad 2 GAHFCGAMM 3 0.570
I-Ad 3 GIGAHFCGA 1 0.504
I-Ad 4 MAINDINGP 11 0.465
I-Ag7 1 INTAENIAC 23 1.564
I-Ag7 2 EINTAENIA 22 1.461
I-Ag7 3 FCGAMMAIN 6 1.246
I-Ag7 4 GIGAHFCGA 1 1.198
RT1.B 1 TEINTAENI 21 0.660
RT1.B 2 VEALSAMLL 48 0.586
RT1.B 3 TLTNDKRVL 62 0.365
RT1.B 4 TAENIACRA 25 0.250

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

vaccines-vaccination-Hydrophobicity

Figure 1: Hydrophobicity plot of antigen protein by Hphob / Welling & al., scale.

vaccines-vaccination-antigen-protein

Figure 2: Hydrophobicity plot of antigen protein by Hphob/ Eisenberg, et al., scale.

vaccines-vaccination-Hydrophobicity

Figure 3: Hydrophobicity plot of antigen protein by Hphob. HPLC /Parker & et al., scale.

vaccines-vaccination-Antigenicity

Figure 4: Antigenicity plot of antigen protein by Hphob. / Rao & Argos, scale.

vaccines-vaccination-Manavalan

Figure 5: Antigenicity plot of antigen protein by Hphob. / Manavalan et al., scale.

Conclusion

An antigen protein from Taenia crassiceps 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 MHCIIligands 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 predicted of antigen protein antigenic peptides to MHC class molecules are important in vaccine development from Taenia crassiceps.

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Citation: Gomase VS, Chitlange NR (2012) Sensitive Quantitative Predictions of MHC Binding Peptides and Fragment Based Peptide Vaccines from Taenia crassiceps. J Vaccines Vaccin 3:131.

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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