Open AccessConverting IL-15 to a superagonist by binding to soluble IL-15Rα
Author(s) -
Mark P. Rubinstein,
Marek Kovář,
Jared F. Purton,
Jae-Ho Cho,
Onur Boyman,
Charles D. Surh,
Jonathan Sprent
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0600240103
Subject(s) - interleukin 15 , cytokine , receptor , chemistry , microbiology and biotechnology , function (biology) , recombinant dna , cd8 , cell growth , in vivo , cell , biology , interleukin , biochemistry , immunology , immune system , gene , genetics
IL-15 is normally presentedin vivo as a cell-associated cytokine bound to IL-15Rα. We show here that the biological activity of soluble IL-15 is much improved after interaction with recombinant soluble IL-15Rα; after injection, soluble IL-15/IL-15Rα complexes rapidly induce strong and selective expansion of memory-phenotype CD8+ cells and natural killer cells. These findings imply that binding of IL-15Rα to IL-15 may create a conformational change that potentiates IL-15 recognition by the βγc receptor on T cells. The enhancing effect of IL-15Rα binding may explain why IL-15 normally functions as a cell-associated cytokine. Significantly, the results with IL-2, a soluble cytokine, are quite different; thus, IL-2 function is markedly inhibited by binding to soluble IL-2Rα.