Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15.
We have recently cloned a novel cytokine, IL-15, with shared bioactivities but no sequence homology with IL-2. We found high affinity IL-15 binding to many cell types, including cells of non-lymphoid origin. Analysis of IL-15 interaction with subunits of the IL-2 receptor (IL-2R) revealed that the alpha subunit was not involved in IL-15 binding. We demonstrated directly in cells transfected with IL-2R subunits that both the beta and gamma chains are required for IL-15 binding and signaling. Hence, IL-15, like IL-2, IL-4 and IL-7, utilizes the common IL-2R gamma subunit found to be defective in X-linked severe combined immunodeficiency in humans. IL-15 is the only cytokine other than IL-2 that has also been shown to share the beta signaling subunit of IL-2R. The differential ability of some cells to bind and respond to IL-2 and IL-15 implies the existence of an additional IL-15-specific component.
Giri
J G
JG
Immunex Research and Development Corporation, Seattle, WA 98101.
Ahdieh
M
M
Eisenman
J
J
Shanebeck
K
K
Grabstein
K
K
Kumaki
S
S
Namen
A
A
Park
L S
LS
Cosman
D
D
Anderson
D
D
D000818:Animals; D002460:Cell Line; D000882:Haplorhini; D006801:Humans; D019409:Interleukin-15; D007378:Interleukins / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D019409:Interleukin-15; D007378:Interleukins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins