Human T cell epitope mapping of the Schistosoma mansoni 14-kDa fatty acid-binding protein using cells from patients living in areas endemic for schistosomiasis.
The development of a defined anti-schistosomiasis vaccine would contribute to the current control strategy mainly because immunization provides long-lasting immunity to the disease. Sm14, one of the six Schistosoma mansoni antigens selected by WHO as a candidate to compose a subunit vaccine against schistosomiasis, has been associated with resistance to S. mansoni infection in human beings and is able to induce protection in the murine model. To identify human T cell epitopes in Sm14, we used the TEPITOPE algorithm to select peptides that would most likely bind to several HLA-DR molecules. In this study, three Sm14 epitopes were selected and produced as synthetic peptides. Human T cell responses from schistosomiasis patients living in endemic areas in Brazil were determined by proliferation assay and IL-5 and IFN-gamma measurements. Differential peptide recognition and cytokine production in response to Sm14 epitopes were observed in individuals resistant to S. mansoni infection versus susceptible individuals. Sm14(32-48) and Sm14(53-69) peptides were preferentially recognized by peripheral blood mononuclear cells (PBMCs) of S. mansoni-resistant individuals, and Sm14(53-69) induced significant production of IFN-gamma. Additionally, Sm14(32-48) and Sm14(53-69) were "promiscuous" peptides, since they were able to induce cellular immune responses in individuals carrying 10 and 8, respectively, of the 11 HLA-DR molecules expressed in the studied population. Among Sm14 synthetic peptides tested in this study, we identified Sm14(32-48) and Sm14(53-69) as promising candidates to compose an anti-schistosomiasis vaccine, since they seem to be related to resistance to human schistosomiasis.
Fonseca
Cristina T
CT
Departamento de Bioquímica e Imunologia, Instituto de Investigação em Imunologia-Instituto do Milênio, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
Cunha-Neto
Edécio
E
Goldberg
Anna C
AC
Kalil
Jorge
J
de Jesus
Amélia R
AR
Carvalho
Edgard M
EM
Correa-Oliveira
Rodrigo
R
Oliveira
Sérgio C
SC
D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D019353:Endemic Diseases; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D012550:Schistosoma mansoni / Q000737:chemistry / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology*
D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D006684:HLA-DR Antigens; D015801:Helminth Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; C068709:SM14 protein, Schistosoma mansoni