60 research outputs found
Dual Mechanism of Interleukin-3 Receptor Blockade by an Anti-Cancer Antibody
SummaryInterleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Here, we report the crystal structure of the IL-3 receptor α chain (IL3Rα) in complex with the anti-leukemia antibody CSL362 that reveals the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5, and IL-13 receptors, adopting unique “open” and classical “closed” conformations. Although extensive mutational analyses of the NTD epitope of CSL362 show minor overlap with the IL-3 binding site, CSL362 only inhibits IL-3 binding to the closed conformation, indicating alternative mechanisms for blocking IL-3 signaling. Significantly, whereas “open-like” IL3Rα mutants can simultaneously bind IL-3 and CSL362, CSL362 still prevents the assembly of a higher-order IL-3 receptor-signaling complex. The discovery of open forms of cytokine receptors provides the framework for development of potent antibodies that can achieve a “double hit” cytokine receptor blockade
Deploying lightweight queue management for improving performance of mobile ad-hoc networks (MANETs)
Engineering design tools for wind diesel systems: presentation and validation of the modular dynamic model
Engineering design tools for wind diesel systems - final report for CEC contract JOUR-0078. Volume 5 - JODYMOD dynamic wind diesel simulation software package : user's guide
Engineering design tools for wind diesel systems - final report for CEC contract JOUR-0078. Volume 2 - JODYMOD dynamic wind diesel simulation software package : model verification
The JODYMOD dynamic wind diesel simulation program part 1: description of the model and its validation
Engineering design tools for wind diesel systems - final report for CEC contract JOUR-0078. Volume 4 - JODYMOD dynamic wind diesel simulation software package: program documentation
Engineering design tools for wind diesel systems: presentation and validation of the logistic modelling package
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