title: A rational approach to select immunogenic peptides that induce IFN-γ response against Toxoplasma gondii in human leukocytes.
abstract: The ideal vaccine to prevent toxoplasmosis in humans would comprise antigens that elicit a protective T cell type 1 response with high IFN-γ production. Here, we report the use of a bioinformatics pipeline to discover peptides based on biochemical characteristics that predict strong IFN-γ response by human leukocytes. We selected peptide sequences that previously were reported to induce IFN-γ to identify the biophysical characteristics that will predict HLA-A*02 high-affinity epitopes. We found that the protein motif pattern FL...L..[VL] was common in previously reported highly immunogenic sequences. We have selected new peptides with a length of 9 residues with affinities from 2 to 21 nM with peptide signal and transmembrane domains and predicted to be cleaved at the proteasome to perform ELISPOT assays with human leukocytes. Within 9 peptides with the highest scores for IFN-γ production, four peptides elicited IFN-γ levels in a range from 252 to 1763 SFC/1e6. Our pipeline uncovered Toxoplasma proteins with peptides that are processed by MHC class 1 in humans. Our results suggest that our rational strategy for the selection of immunogenic epitopes could be used to select peptides as candidates for inclusion in epitope-based vaccines.
authors.affiliation: Grupo GEPAMOL, Centro de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Universidad del Quindío, Armenia, Colombia.
authors.forename: Néstor I
authors.initials: NI
authors.lastname: Cardona
authors.affiliation: Grupo GEPAMOL, Centro de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Universidad del Quindío, Armenia, Colombia.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Moncada
authors.affiliation: Grupo GEPAMOL, Centro de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Universidad del Quindío, Armenia, Colombia. Electronic address: gepamol2@uniquindio.edu.co.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Gómez-Marin
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D056510:Position-Specific Scoring Matrices; D011487:Protein Conformation; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010455:Peptides; D007371:Interferon-gamma
keywords: ELISPOT; Immunoinformatics; Interferon gamma; Peptides; Vaccine