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Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}


IL-15 is normally presented in vivo as a cell-associated cytokine bound to IL-15Ralpha. We show here that the biological activity of soluble IL-15 is much improved after interaction with recombinant soluble IL-15Ralpha; after injection, soluble IL-15/IL-15Ralpha complexes rapidly induce strong and selective expansion of memory-phenotype CD8(+) cells and natural killer cells. These findings imply that binding of IL-15Ralpha to IL-15 may create a conformational change that potentiates IL-15 recognition by the betagamma(c) receptor on T cells. The enhancing effect of IL-15Ralpha 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-2Ralpha.

Type Journal
ISBN 0027-8424 (Print)
Authors Rubinstein, M. P.;Kovar, M.;Purton, J. F.;Cho, J. H.;Boyman, O.;Surh, C. D.;Sprent, J. :
Garvan Authors Prof Jonathan Sprent
Publisher Name PNAS
Published Date 2006-01-01 00:00:00
Published Volume 103
Published Issue 24
Published Pages 9166-71
Status Published In-print
OpenAccess Link Rubinstein PNAS.pdf