title: In silico prediction of binding of promiscuous peptides to multiple MHC class-II molecules identifies the Th1 cell epitopes from secreted and transmembrane proteins of Schistosoma japonicum in BALB/c mice.
abstract: It has not so far been possible to identify rapidly and effectively the anti-schistosomiasis Th cell epitopes that are capable of simulating IFN-γ (Interferon-gamma)-mediated Th1-type protective immunity in response to radiation-attenuated schistosome cercaria. With the advance of the omics studies of schistosomes, an approach that used reverse vaccinology probably resolved the above problems. In this "proof-of-principle" study, first, we selected 31 secreted or transmembrane protein sequences sampled from sequences of the transcriptome of Schistosoma japonicum, and analyzed characteristics of these proteins by using conventional bioinformatics tools. Second, putative promiscuous Th cell epitopes within these proteins were predicted using three to four different immuno-informatics algorithms for the prediction of MHC (Major Histocompatibility Complex) class-II binding peptides. We predicted using these in silico approaches promiscuous Th cell epitopes that are capable of binding to both murine and human MHC class-II molecules. To validate our in silico prediction experimentally, BALB/c mice were immunized with the five predicted peptides, and the proliferative responses and cytokine production of lymphocytes from the immunized BALB/c mice were assessed in vitro by modified MTT (Methyl Thiazolyl Tetrazolium), ELISA (Enzyme-linked Immunosorbent Assay) and flow cytometry methods. The results showed that two of the five predicted peptides could induce a Th1-type response in vitro. These results suggest that promiscuous Th1 cell epitopes from secreted or transmembrane proteins of S. japonicum can be identified using a strategy of reverse vaccinology.
authors: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology, Ministry of Agriculture of China, Shanghai 200241, China.
authors: Ben Peng
authors: BP
authors: Zhao
authors: Lei
authors: L
authors: Chen
authors: Yan Li
authors: YL
authors: Zhang
authors: Jian Mei
authors: JM
authors: Yang
authors: Kan
authors: K
authors: Jia
authors: Chuan Yu
authors: CY
authors: Sui
authors: Chun Xiu
authors: CX
authors: Yuan
authors: Jiao Jiao
authors: JJ
authors: Lin
authors: Xin Gang
authors: XG
authors: Feng
mesh_terms: D000465:Algorithms; D000818:Animals; D000947:Antigens, Helminth / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D019295:Computational Biology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D012549:Schistosoma japonicum / Q000235:genetics / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology; D020539:Sequence Analysis, Protein; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D011994:Recombinant Proteins