Soluble Interleukin-15 Receptor α (IL-15Rα)-sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rβ/γ HYPERAGONIST IL-15.IL-15Rα FUSION PROTEINS - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Biological Chemistry Year : 2006

Soluble Interleukin-15 Receptor α (IL-15Rα)-sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rβ/γ HYPERAGONIST IL-15.IL-15Rα FUSION PROTEINS

Abstract

Interleukin-15 (IL-15) is crucial for the generation of multiple lymphocyte subsets (natural killer (NK), NK-T cells, and memory CD8 T cells), and transpresentation of IL-15 by monocytes and dendritic cells has been suggested to be the dominant activating process of these lymphocytes. We have previously shown that a natural soluble form of IL-15Rα chain corresponding to the entire extracellular domain of IL-15Rα behaves as a high affinity IL-15 antagonist. In sharp contrast with this finding, we demonstrate in this report that a recombinant, soluble sushi domain of IL-15Rα, which bears most of the binding affinity for IL-15, behaves as a potent IL-15 agonist by enhancing its binding and biological effects (proliferation and protection from apoptosis) through the IL-15Rβ/␥ heterodimer, whereas it does not affect IL-15 binding and function of the tripartite IL-15Rα/β/γ membrane receptor. Our results suggest that, if naturally produced, such soluble sushi domains might be involved in the IL-15 transpresentation mechanism. Fusion proteins (RLI and ILR), in which IL-15 and IL-15Rα-sushi are attached by a flexible linker, are even more potent than the combination of IL-15 plus sIL-15Rα-sushi. After binding to IL-15Rβ/␥, RLI is internalized and induces a biological response very similar to the IL-15 high affinity response. Such hyper-IL-15 fusion proteins appear to constitute potent adjuvants for the expansion of lymphocyte subsets.
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inserm-02442379 , version 1 (16-01-2020)

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Erwan Mortier, Agnès Quéméner, Patricia Vusio, Inken Lorenzen, Yvan Boublik, et al.. Soluble Interleukin-15 Receptor α (IL-15Rα)-sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rβ/γ HYPERAGONIST IL-15.IL-15Rα FUSION PROTEINS. Journal of Biological Chemistry, 2006, 281 (3), pp.1612. ⟨10.1074/jbc.M508624200⟩. ⟨inserm-02442379⟩
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