Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Proliferation
-
Humans
-
Interleukin-15 / genetics
-
Interleukin-15 / metabolism*
-
Interleukin-2 / genetics
-
Interleukin-2 / metabolism
-
Interleukin-2 Receptor alpha Subunit
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Protein Binding
-
Protein Isoforms / genetics
-
Protein Isoforms / metabolism*
-
Receptors, Interleukin-15
-
Receptors, Interleukin-2 / genetics
-
Receptors, Interleukin-2 / metabolism*
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
Substances
-
IL15RA protein, human
-
IL2RA protein, human
-
Il15ra protein, mouse
-
Il2ra protein, mouse
-
Interleukin-15
-
Interleukin-2
-
Interleukin-2 Receptor alpha Subunit
-
Protein Isoforms
-
Receptors, Interleukin-15
-
Receptors, Interleukin-2
-
Recombinant Fusion Proteins
-
Recombinant Proteins