Interleukin 15 and its receptor.
Interleukin 15 (IL-15) is a member of the four-helix bundle cytokine family that shares many in vitro biological activities with IL-2. Previous work demonstrated that IL-15 utilizes the beta and gamma chains of the IL-2 receptor (IL-2R), and that these are essential for IL-15-mediated signal transduction. However, several lines of evidence indicated the existence of an additional, IL-15-specific receptor component. An IL-15 binding chain was identified on a murine T cell clone, and direct expression cloning was used to isolate the corresponding cDNA. The predicted structure of this protein shows sequence similarity to the IL-2R alpha chain. Transfection of this cDNA into a murine, IL-3-dependent myeloid cell line, 32D-01, conferred IL-15 binding and, together with transfection of the IL-2R beta chain, rendered the cells responsive to IL-15 stimulation. This experiment confirmed that the IL-15 binding chain is part of the IL-15 receptor, and it is designated as the IL-15R alpha subunit. The expression pattern of the IL-15R alpha mRNA is distinct from that of IL-2R alpha mRNA. Recombinant expression of a soluble form of IL-15R alpha demonstrated that it is a potent inhibitor of IL-15 biological activity.
Cosman
D
D
Immunex Research and Development Corporation, Seattle, WA 98101, USA.
Kumaki
S
S
Ahdieh
M
M
Eisenman
J
J
Grabstein
K H
KH
Paxton
R
R
DuBose
R
R
Friend
D
D
Park
L S
LS
Anderson
D
D
D000818:Animals; D006801:Humans; D019409:Interleukin-15; D007378:Interleukins / Q000276:immunology*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*
C508024:IL15RA protein, human; D019409:Interleukin-15; D007378:Interleukins; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2