highly active microbial phosphoantigen induces rapid yet sustained mekerk- and pi-3kakt-mediated signal transduction in anti-tumor human γδ t-cells高活性微生物phosphoantigen诱发快速但持续mekerk - pi-3kakt-mediated信号转导在人类γδt细胞抗肿瘤.pdfVIP

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highly active microbial phosphoantigen induces rapid yet sustained mekerk- and pi-3kakt-mediated signal transduction in anti-tumor human γδ t-cells高活性微生物phosphoantigen诱发快速但持续mekerk - pi-3kakt-mediated信号转导在人类γδt细胞抗肿瘤.pdf

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highly active microbial phosphoantigen induces rapid yet sustained mekerk- and pi-3kakt-mediated signal transduction in anti-tumor human γδ t-cells高活性微生物phosphoantigen诱发快速但持续mekerk - pi-3kakt-mediated信号转导在人类γδt细胞抗肿瘤

Highly Active Microbial Phosphoantigen Induces Rapid yet Sustained MEK/Erk- and PI-3K/Akt-Mediated Signal Transduction in Anti-Tumor Human cd T-Cells 1,4. 1,4. 2 1,4 3 Daniel V. Correia , Francisco d’Orey , Bruno A. Cardoso , Telma Lanc¸a , Ana R. Grosso , Ana 1,4 2 ˜ 2 1,4 deBarros , Leila R. Martins , Joao T. Barata , Bruno Silva-Santos * 1 Molecular Immunology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal, 2 Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal, 3 Cellular Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina ˆ da Universidade de Lisboa, Lisbon, Portugal, 4 Instituto Gulbenkian de Ciencia, Oeiras, Portugal Abstract Background: The unique responsiveness of Vc9Vd2 T-cells, the major cd subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current cd T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human cd T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR)-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vc9Vd2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E)