title: Prediction of CD8+ Epitopes in Leishmania braziliensis Proteins Using EPIBOT: In Silico Search and In Vivo Validation.
abstract: BACKGROUND
  Leishmaniasis is caused by intracellular Leishmania parasites that induce a T-cell mediated response associated with recognition of CD4+ and CD8+ T cell Line 1Lineepitopes. Identification of CD8+ antigenic determinants is crucial for vaccine and therapy development. Herein, we developed an open-source software dedicated to search and compile data obtained from currently available on line prediction algorithms.
  
  
  RESULTS
  We developed a two-phase algorithm and implemented in an open source software called EPIBOT, that consolidates the results obtained with single prediction algorithms, generating a final output in which epitopes are ranked. EPIBOT was initially trained using a set of 831 known epitopes from 397 proteins from IEDB. We then screened 63 Leishmania braziliensis vaccine candidates with the EPIBOT trained tool to search for CD8+ T cell epitopes. A proof-of-concept experiment was conducted with the top eight CD8+ epitopes, elected by EPIBOT. To do this, the elected peptides were synthesized and validated for their in vivo cytotoxicity. Among the tested epitopes, three were able to induce lysis of pulsed-target cells.
  
  
  CONCLUSIONS
  Our results show that EPIBOT can successfully search across existing prediction tools, generating a compiled list of candidate CD8+ epitopes. This software is fast and a simple search engine that can be customized to search over different MHC alleles or HLA haplotypes.
authors.affiliation: Departmento de Tecnologia, Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, DTEC-Módulo 3, 44036-900, Feira de Santana, BA, Brazil.
authors.forename: Angelo
authors.initials: A
authors.lastname: Duarte
authors.affiliation: CPqGM-FIOCRUZ, R. Waldemar Falcão, 121, 40296-710, Salvador, BA, Brazil.
authors.forename: Artur T L
authors.initials: AT
authors.lastname: Queiroz
authors.affiliation: Departmento de Tecnologia, Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, DTEC-Módulo 3, 44036-900, Feira de Santana, BA, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Tosta
authors.affiliation: CPqGM-FIOCRUZ, R. Waldemar Falcão, 121, 40296-710, Salvador, BA, Brazil.
authors.forename: Augusto M
authors.initials: AM
authors.lastname: Carvalho
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho, 373 Bloco D, sala 35, Cidade Universitária, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos Henrique
authors.initials: CH
authors.lastname: Barbosa
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho, 373 Bloco D, sala 35, Cidade Universitária, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Maria
authors.initials: M
authors.lastname: Bellio
authors.affiliation: CPqGM-FIOCRUZ, R. Waldemar Falcão, 121, 40296-710, Salvador, BA, Brazil; Instituto de Investigação em Imunologia, São Paulo, Brazil.
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
authors.affiliation: CPqGM-FIOCRUZ, R. Waldemar Falcão, 121, 40296-710, Salvador, BA, Brazil; Instituto de Investigação em Imunologia, São Paulo, Brazil.
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007892:Leishmania braziliensis / Q000378:metabolism*; D007896:Leishmaniasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism; D012984:Software
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D015800:Protozoan Proteins