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Immunobiology ; 220(12): 1337-42, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26210043

RESUMEN

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.


Asunto(s)
Mapeo Epitopo , Epítopos de Linfocito T/inmunología , Interferón gamma/biosíntesis , Leucocitos/inmunología , Leucocitos/metabolismo , Péptidos/inmunología , Toxoplasma/inmunología , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Biología Computacional/métodos , Ensayo de Immunospot Ligado a Enzimas , Mapeo Epitopo/métodos , Epítopos de Linfocito T/química , Antígeno HLA-A2/química , Antígeno HLA-A2/inmunología , Prueba de Histocompatibilidad , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Modelos Moleculares , Péptidos/química , Posición Específica de Matrices de Puntuación , Conformación Proteica , Toxoplasmosis/inmunología , Toxoplasmosis/metabolismo , Toxoplasmosis/parasitología
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