4 research outputs found

    HLA-DR-restricted peptides identified in the Nef protein can induce HIV type 1-specific IL-2/IFN-gamma-secreting CD4+ and CD4+ /CD8+ T cells in humans after lipopeptide vaccination.

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    International audienceWe screened the Neflaiprotein to identify new HLA-DR-restricted epitopes, because this small protein is expressed early during infection, and specific CD4(+) T cells are critical for effective immunity in HIV-1 infection. We synthesized a set of peptides that covers the sequence of the Nef protein, and performed binding assays using 10 common HLA-DR molecules. We defined four large regions in this protein able to bind very efficiently to eight HLADR molecules. We took advantage of healthy volunteers immunized with an HIV-1 lipopeptide vaccine that contains three of the four HLA DR-restricted regions to investigate their capacities to stimulate T cells. In 11 vaccinated volunteers, typed for their class II molecules, we were able to correlate sequences of the vaccine displaying binding activities to specific HLA-DR molecules and the induction of CD4(+) T cell proliferation. To identify potential HLA-DR epitopes, we synthesized 31 15-mer peptides and showed that 26 bound to one or more HLA-DR molecules. Interestingly, 12 of the 26 15-mer peptides identified are included in the sequence of lipopeptides. We used IFN-gamma ELISPOT and flow cytometer assays to investigate the capacity of these potential CD4(+) T cell epitopes to induce specific T cell responses. We showed that seven of these peptides were able to stimulate HIV-specific T cell responses in five of six tested volunteers. These cells are Nef-specific CD4(+) and CD4(+) CD8(+) T cells secreting IL-2/INF-gamma or IL-2 alone. To conclude, these 26 Nef HLA-DR-restricted peptides could be helpful to better evaluate CD4(+) deficiencies in HIV infection and, for new vaccine designs

    Data from: Ecological speciation in sympatric palms: 1. Gene expression, selection and pleiotropy

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    Ecological speciation requires divergent selection, reproductive isolation, and a genetic mechanism to link the two. We examined the role of gene expression and coding sequence evolution in this process using two species of Howea palms that have diverged sympatrically on Lord Howe Island, Australia. These palms are associated with distinct soil types and have displaced flowering times, representing an ideal candidate for ecological speciation. We generated large amounts of RNA-Seq data from multiple individuals and tissue types collected on the island from each of the two species. We found that differentially expressed loci as well as those with divergent coding sequences between Howea species were associated with known ecological and phenotypic differences, including response to salinity, drought, pH and flowering time. From these loci we identified potential ‘ecological speciation genes’, and further validate their effect on flowering time by knocking out orthologous loci in a model plant species. Finally, we put forward six plausible ecological speciation loci, providing support for the hypothesis that pleiotropy could help to overcome the antagonism between selection and recombination during speciation with gene flow
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