title: Improved proteomic approach for the discovery of potential vaccine targets in Trypanosoma cruzi.
abstract: Chagas disease, caused by Trypanosoma cruzi, is a devastating parasitic infection affecting millions of people. Although many efforts have been made for the development of immunotherapies, there is no available vaccine against this deadly infection. One major hurdle for the rational approach to develop a T. cruzi vaccine is the limited information about the proteins produced by different phylogenetic lineages, strains, and stages of the parasite. Here, we have adapted a 1D nanoHPLC system to perform online 2D LC-MS/MS, using the autosampler to inject the eluting salt solutions in the first dimension separation. The application of this methodology for the proteomic analysis of the infective trypomastigote stage of T. cruzi led to the identification of 1448 nonredundant proteins. Furthermore, about 14% of the identified sequences comprise surface proteins, most of them glycosylphosphatidylinositol (GPI)-anchored and related to parasite pathogenesis. Immunoinformatic analysis revealed thousands of potential peptides with predicted high-binding affinity for major histocompatibility complex (MHC) class I and II molecules. The high diversity of proteins expressed on the trypomastigote surface may have many implications for host-cell invasion and immunoevasion mechanisms triggered by the parasite. Finally, we performed a rational approach to filter potential T-cell epitopes that could be further tested and validated for development of a Chagas disease vaccine.
authors: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, 500 West University Avenue, El Paso, Texas 79902, United States. esnakayasu@miners.utep.edu
authors: Ernesto S
authors: ES
authors: Nakayasu
authors: Tiago J P
authors: TJ
authors: Sobreira
authors: Rafael
authors: R
authors: Torres
authors: Luciane
authors: L
authors: Ganiko
authors: Paulo S L
authors: PS
authors: Oliveira
authors: Alexandre F
authors: AF
authors: Marques
authors: Igor C
authors: IC
authors: Almeida
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy / Q000517:prevention & control; D002522:Chlorocebus aethiops; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D003198:Computer Simulation; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D010446:Peptide Fragments / Q000737:chemistry; D020543:Proteome / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016052:Protozoan Vaccines; D053719:Tandem Mass Spectrometry; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D058851:GPI-Linked Proteins; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D020543:Proteome; D015800:Protozoan Proteins; D016052:Protozoan Vaccines