IL17eScan: A Tool for the Identification of Peptides Inducing IL-17 Response

IL-17 cytokines are pro-inflammatory cytokines and are crucial in host defense against various microbes. Induction of these cytokines by microbial antigens has been investigated in the case of ischemic brain injury, gingivitis, candidiasis, autoimmune myocarditis, etc. In this study, we have investigated the ability of amino acid sequence of antigens to induce IL-17 response using machine-learning approaches. A total of 338 IL-17-inducing and 984 IL-17 non-inducing peptides were retrieved from Immune Epitope Database. 80% of the data were randomly selected as training dataset and rest 20% as validation dataset. To predict the IL-17-inducing ability of peptides/protein antigens, different sequence-based machine-learning models were developed. The performance of support vector machine (SVM) and random forest (RF) was compared with different parameters to predict IL-17-inducing epitopes (IIEs). The dipeptide composition-based SVM-model displayed an accuracy of 82.4% with Matthews correlation coefficient = 0.62 at polynomial (t = 1) kernel on 10-fold cross-validation and outperformed RF. Amino acid residues Leu, Ser, Arg, Asn, and Phe and dipeptides LL, SL, LK, IL, LI, NL, LR, FK, SF, and LE are abundant in IIEs. The present tool helps in the identification of IIEs using machine-learning approaches. The induction of IL-17 plays an important role in several inflammatory diseases, and identification of such epitopes would be of great help to the immunologists. It is freely available at http://metagenomics.iiserb.ac.in/IL17eScan/ and http://metabiosys.iiserb.ac.in/IL17eScan/.

[1]  S. Gaffen.  The role of interleukin-17 in the pathogenesis of rheumatoid arthritis , 2009, Current rheumatology reports.

[2]  Harinder Singh,et al.  Improved Method for Linear B-Cell Epitope Prediction Using Antigen’s Primary Sequence , 2013, PloS one.

[3]  Vineet K. Sharma,et al.  Woods: A fast and accurate functional annotator and classifier of genomic and metagenomic sequences. , 2015, Genomics.

[4]  Deborah Hix,et al.  The immune epitope database (IEDB) 3.0 , 2014, Nucleic Acids Res..

[5]  Gajendra P. S. Raghava,et al.  AlgPred: prediction of allergenic proteins and mapping of IgE epitopes , 2006, Nucleic Acids Res..

[6]  P. Tak,et al.  Effects of AIN457, a Fully Human Antibody to Interleukin-17A, on Psoriasis, Rheumatoid Arthritis, and Uveitis , 2010, Science Translational Medicine.

[7]  R. Broaddus,et al.  Regulation of inflammatory responses by IL-17F , 2008, The Journal of experimental medicine.

[8]  Jonathan L. Linehan,et al.  Focused Specificity of Intestinal Th17 Cells towards Commensal Bacterial Antigens , 2014, Nature.

[9]  Gajendra P. S. Raghava,et al.  Computer-aided designing of immunosuppressive peptides based on IL-10 inducing potential , 2017, Scientific Reports.

[10]  Gajendra P.S. Raghava,et al.  A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes , 2007, Journal of Biosciences.

[11]  Sudipto Saha,et al.  Prediction methods for B-cell epitopes. , 2007, Methods in molecular biology.

[12]  M. Costalonga,et al.  Identification of gingipain-specific I-Ab-restricted CD4+ T cells following mucosal colonization with Porphyromonas gingivalis in C57BL/6 mice , 2013, Molecular oral microbiology.

[13]  Vasant Honavar,et al.  Predicting flexible length linear B-cell epitopes. , 2008, Computational systems bioinformatics. Computational Systems Bioinformatics Conference.

[14]  W. Jin,et al.  IL-17 cytokines in immunity and inflammation , 2013, Emerging Microbes & Infections.

[15]  Praveen Kumar Sharma,et al.  Prediction and characterization of helper T‐cell epitopes from pneumococcal surface adhesin A , 2014, Immunology.

[16]  C. Massilamany,et al.  Identification of novel mimicry epitopes for cardiac myosin heavy chain-α that induce autoimmune myocarditis in A/J mice. , 2011, Cellular immunology.

[17]  Dongwon Lee,et al.  kmer-SVM: a web server for identifying predictive regulatory sequence features in genomic data sets , 2013, Nucleic Acids Res..

[18]  Danh C. Do,et al.  The Role of Bacterial Biofilms in Chronic Infections , 2014 .

[19]  Hae-Jin Hu,et al.  Improved protein secondary structure prediction using support vector machine with a new encoding scheme and an advanced tertiary classifier , 2004, IEEE Transactions on NanoBioscience.

[20]  Monika Schneider,et al.  NLRP3 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis by Mediating Th1 and Th17 Responses , 2010, The Journal of Immunology.

[21]  T. Mcclanahan,et al.  IL-23 drives a pathogenic T cell population that induces autoimmune inflammation , 2005, The Journal of experimental medicine.

[22]  S. Nakae,et al.  IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis1 , 2006, The Journal of Immunology.

[23]  H. Uenishi,et al.  Fine structure of a virus-encoded helper T-cell epitope expressed on FBL-3 tumor cells , 1994, Journal of virology.

[24]  澤井 直樹.  Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model , 1999 .

[25]  Roger Kurlan,et al.  Current Concepts , 2022 .

[26]  M. D. Dal Canto,et al.  Epitope-Specific CD8+ T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis , 2012, Journal of Virology.

[27]  P. Mahadevan,et al.  An overview , 2007, Journal of Biosciences.

[28]  Keun-Hwa Jung,et al.  Anti-LGI1 Limbic Encephalitis Presented with Atypical Manifestations , 2013, Experimental neurobiology.

[29]  G. Tsokos,et al.  Interleukin‐17 and systemic lupus erythematosus: current concepts , 2009, Clinical and experimental immunology.

[30]  R. Ward,et al.  Identification of an immunodominant CD4+ T cell epitope in the VP6 protein of rotavirus following intranasal immunization of BALB/c mice. , 2007, Virology.

[31]  A. Sette,et al.  Novel pan-DR-binding T cell epitopes of adenovirus induce pro-inflammatory cytokines and chemokines in healthy donors. , 2006, International immunology.

[32]  Vineet K. Sharma,et al.  MP3: A Software Tool for the Prediction of Pathogenic Proteins in Genomic and Metagenomic Data , 2014, PloS one.

[33]  Y. Yamaoka,et al.  IL‐17 is Involved in Helicobacter pylori‐Induced Gastric Inflammatory Responses in a Mouse Model , 2008, Helicobacter.

[34]  Gajendra P.S. Raghava,et al.  Prediction of CTL epitopes using QM, SVM and ANN techniques. , 2004, Vaccine.

[35]  Gajendra PS Raghava,et al.  Designing of interferon-gamma inducing MHC class-II binders , 2013, Biology Direct.

[36]  M. Ono,et al.  A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus , 2012, Arthritis Research & Therapy.

[37]  Rahul Kumar,et al.  Peptide toxicity prediction. , 2015, Methods in molecular biology.

[38]  M. Romano,et al.  Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa1 , 2000, The Journal of Immunology.

[39]  Ying Wang,et al.  A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 , 2005, Nature Immunology.

[40]  E. Choy.  Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. , 2012, Rheumatology.

[41]  Manoj Bhasin,et al.  Analysis and prediction of affinity of TAP binding peptides using cascade SVM , 2004, Protein science : a publication of the Protein Society.

[42]  Gajendra PS Raghava,et al.  Identification of B-cell epitopes in an antigen for inducing specific class of antibodies , 2013, Biology Direct.

[43]  S. Miller,et al.  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. , 2008, Journal of autoimmunity.

[44]  A. Hamzaoui,et al.  Cytokine profile in Behçet's disease patients , 2002, Scandinavian journal of rheumatology.

[45]  Federica Sallusto,et al.  Heterogeneity of Human CD4(+) T Cells Against Microbes. , 2016, Annual review of immunology.

[46]  M. Zandi,et al.  Defining and treating leucine-rich glioma inactivated 1 antibody associated autoimmunity. , 2013, Brain : a journal of neurology.

[47]  Eric G. Pamer,et al.  Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδT cells , 2016, Nature Medicine.

[48]  Irini A. Doytchinova,et al.  AllerTOP - a server for in silico prediction of allergens , 2013, BMC Bioinformatics.

[49]  S. Yadav,et al.  Biofilms: microbes and disease. , 2008, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[50]  C. Wong,et al.  Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus , 2000, Lupus.

[51]  C. Sasakawa,et al.  Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. , 2009, Immunity.

[52]  V. Taneja,et al.  HLA Class II Molecules Influence Susceptibility versus Protection in Inflammatory Diseases by Determining the Cytokine Profile , 2013, The Journal of Immunology.

[53]  Gajendra P. S. Raghava,et al.  Prediction of allergenic proteins and mapping of IgE epitopes in allergens , 2007 .

[54]  Urmila Kulkarni-Kale,et al.  T-cell epitope prediction methods: an overview. , 2014, Methods in molecular biology.

[55]  Vladimir Vacic,et al.  Two Sample Logo: a graphical representation of the differences between two sets of sequence alignments , 2006, Bioinform..