title: An immunoinformatic approach for identification of Trypanosoma cruzi HLA-A2-restricted CD8(+) T cell epitopes.
abstract: Chagas disease is a major neglected tropical disease caused by persistent chronic infection with the protozoan parasite Trypanosoma cruzi. An estimated 8 million people are infected with T. cruzi, however only 2 drugs are approved for treatment and no vaccines are available. Thus there is an urgent need to develop vaccines and new drugs to prevent and treat Chagas disease. In this work, we identify T cell targets relevant for human infection with T. cruzi. The trans-sialidase (TS) gene family is a large family of homologous genes within the T. cruzi genome encoding over 1,400 members. There are 12 highly conserved TS gene family members which encode enzymatically active TS (functional TS; F-TS), while the remaining TS family genes are less conserved, enzymatically inactive and have been hypothesized to be involved in immune evasion (non-functional TS; NF-TS). We utilized immunoinformatic tools to identify HLA-A2-restricted CD8(+) T cell epitopes conserved within F-TS family members and NF-TS gene family members. We also utilized a whole-genome approach to identify T cell epitopes present within genes which have previously been shown to be expressed in life stages relevant for human infection (Non-TS genes). Thirty immunogenic HLA-A2-restricted CD8(+) T cell epitopes were identified using IFN-γ ELISPOT assays after vaccination of humanized HLA-A2 transgenic mice with mature dendritic cells pulsed with F-TS, NF-TS, and Non-TS peptide pools. The immunogenic HLA-A2-restricted T cell epitopes identified in this work may serve as potential components of an epitope-based T cell targeted vaccine for Chagas disease.
authors.affiliation: a Division of Infectious Diseases, Allergy, and Immunology; Department of Internal Medicine; Saint Louis University ; Saint Louis , MO USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Eickhoff
authors.forename: Daniel
authors.initials: D
authors.lastname: Van Aartsen
authors.forename: Frances E
authors.initials: FE
authors.lastname: Terry
authors.forename: Sheba K
authors.initials: SK
authors.lastname: Meymandi
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Traina
authors.forename: Salvador
authors.initials: S
authors.lastname: Hernandez
authors.forename: William D
authors.initials: WD
authors.lastname: Martin
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.forename: Annie S
authors.initials: AS
authors.lastname: De Groot
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019295:Computational Biology / Q000379:methods*; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008822:Mice, Transgenic; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015789:HLA-A2 Antigen; D016052:Protozoan Vaccines; D007371:Interferon-gamma; C069715:trans-sialidase; D009439:Neuraminidase
keywords: CD8+ T cell; Chagas disease; Human leukocyte antigen (HLA); bioinformatics; epitope; immunity; protozoan parasite; vaccine