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A computational high-throughput screening approach of iNKT-agonists: a novel tool to find optimized iNKT cell ligands

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Abstract
Depending on the environment and the activating glycolipids, iNKT cells are known to induce T-helper 1 and/or T-helper 2 cytokines. This highly versatile nature makes these innate-like cells very interesting targets for immunomodulation. As many pathologies as well as physiological ageing are associated with altered immune responses, iNKT cells could play a role in new therapies. Many analogs of the glycolipid alpha-galactosylceramide (a-GalCer) are known to activate iNKT-cells through their interaction with CD1d-expressing antigen-presenting cells, inducing the release of Th1 and/or Th2 cytokines. The design of iNKT cell ligands with selective Th1 and Th2 properties requires refined structural insights. Therefore, the chemical space of 333 currently known iNKT activators, including several newly tested analogs, was visualized by more than 3000 chemical descriptors which were calculated for each individual analog. The immunological responses consisted of four different cytokines in five different test-systems. With these two information-sets, structure-activity models were developed using a system biology computational approach. We present highly sensitive and specific predictive models that can be further exploited as high-throughput instruments to in-silico screen potential glycolipids, thereby reducing the attrition rate.
Keywords
iNKT, QSAR

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Chicago
De Spiegeleer, Anton, Evelien Wynendaele, Sofie Stalmans, Nele Van Den Noortgate, Matthias Vandekerckhove, Serge Van Calenbergh, SANDRINE ASPESLAGH, Koen Venken, and Dirk Elewaut. 2013. “A Computational High-throughput Screening Approach of iNKT-agonists: a Novel Tool to Find Optimized iNKT Cell Ligands.” In CD1 and NKT Cells, 7th International Symposium, Abstracts.
APA
De Spiegeleer, A., Wynendaele, E., Stalmans, S., Van Den Noortgate, N., Vandekerckhove, M., Van Calenbergh, S., ASPESLAGH, S., et al. (2013). A computational high-throughput screening approach of iNKT-agonists: a novel tool to find optimized iNKT cell ligands. CD1 and NKT Cells, 7th International symposium, Abstracts. Presented at the 7th International symposium on CD1 and NKT Cells.
Vancouver
1.
De Spiegeleer A, Wynendaele E, Stalmans S, Van Den Noortgate N, Vandekerckhove M, Van Calenbergh S, et al. A computational high-throughput screening approach of iNKT-agonists: a novel tool to find optimized iNKT cell ligands. CD1 and NKT Cells, 7th International symposium, Abstracts. 2013.
MLA
De Spiegeleer, Anton, Evelien Wynendaele, Sofie Stalmans, et al. “A Computational High-throughput Screening Approach of iNKT-agonists: a Novel Tool to Find Optimized iNKT Cell Ligands.” CD1 and NKT Cells, 7th International Symposium, Abstracts. 2013. Print.
@inproceedings{4141880,
  abstract     = {Depending on the environment and the activating glycolipids, iNKT cells are known to induce T-helper 1 and/or T-helper 2 cytokines. This highly versatile nature makes these innate-like cells very interesting targets for immunomodulation. As many pathologies as well as physiological ageing are associated with altered immune responses, iNKT cells could play a role in new therapies. Many analogs of the glycolipid alpha-galactosylceramide (a-GalCer) are known to activate iNKT-cells through their interaction with CD1d-expressing antigen-presenting cells, inducing the release of Th1 and/or Th2 cytokines. The design of iNKT cell ligands with selective Th1 and Th2 properties requires refined structural insights. Therefore, the chemical space of 333 currently known iNKT activators, including several newly tested analogs, was visualized by more than 3000 chemical descriptors which were calculated for each individual analog. The immunological responses consisted of four different cytokines in five different test-systems. With these two information-sets, structure-activity models were developed using a system biology computational approach. We present highly sensitive and specific predictive models that can be further exploited as high-throughput instruments to in-silico screen potential glycolipids, thereby reducing the attrition rate.},
  author       = {De Spiegeleer, Anton and Wynendaele, Evelien and Stalmans, Sofie and Van Den Noortgate, Nele and Vandekerckhove, Matthias and Van Calenbergh, Serge and ASPESLAGH, SANDRINE and Venken, Koen and Elewaut, Dirk},
  booktitle    = {CD1 and NKT Cells, 7th International symposium, Abstracts},
  language     = {eng},
  location     = {Tours, France},
  title        = {A computational high-throughput screening approach of iNKT-agonists: a novel tool to find optimized iNKT cell ligands},
  year         = {2013},
}