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Seeking an alternative for the control of disease, the World Health Organization funded the genome sequencing of the major species related to schistosomiasis to identify potential vaccines and therapeutic targets. Therefore, the aim of this work was to select T and B\u2010cell epitopes from <jats:italic>Schistosoma mansoni<\/jats:italic> through computational analyses and evaluate the immunological potential of epitopes <jats:italic>in vitro<\/jats:italic>. Extracellular regions of membrane proteins from the <jats:italic>Schistosoma mansoni<\/jats:italic> were used to predict promiscuous epitopes with affinity to different human Major Histocompatibility Class II (MHCII) molecules by bioinformatics analysis. The three\u2010dimensional structure of selected epitopes was constructed and used in molecular docking to verify the interaction with murine MHCII H2\u2010IA<jats:sup>b<\/jats:sup>. In this process, four epitopes were selected and synthesized to assess their ability to stimulate proliferation of CD4<jats:sup>+<\/jats:sup> T lymphocytes in mice splenocyte cultures. The results showed that Sm041370 and Sm168240 epitopes induced significant cell proliferation. Additionally, the four epitopes were used as antigens in the Indirect Enzyme\u2010Linked Immunosorbent Assay (ELISA) to assess the recognition by serum from individuals infected with <jats:italic>Schistosoma mansoni<\/jats:italic>. Sm140560, Sm168240, and Sm041370 epitopes were recognized by infected individuals IgG antibodies. Therefore, Sm041370 and Sm168240 epitopes that stood out in <jats:italic>in silico<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> analyses could be promising antigens in schistosomiasis vaccine development or diagnostic kits. \u00a9 2017 American Institute of Chemical Engineers Biotechnol. 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