Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.
Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.
Parrish-Novak
J
J
Department of Functional Cloning, ZymoGenetics, Inc., Seattle, Washington 98102, USA.
Dillon
S R
SR
Nelson
A
A
Hammond
A
A
Sprecher
C
C
Gross
J A
JA
Johnston
J
J
Madden
K
K
Xu
W
W
West
J
J
Schrader
S
S
Burkhead
S
S
Heipel
M
M
Brandt
C
C
Kuijper
J L
JL
Kramer
J
J
Conklin
D
D
Presnell
S R
SR
Berry
J
J
Shiota
F
F
Bort
S
S
Hambly
K
K
Mudri
S
S
Clegg
C
C
Moore
M
M
Grant
F J
FJ
Lofton-Day
C
C
Gilbert
T
T
Rayond
F
F
Ching
A
A
Yao
L
L
Smith
D
D
Webster
P
P
Whitmore
T
T
Maurer
M
M
Kaushansky
K
K
Holly
R D
RD
Foster
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D019013:CD40 Antigens / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D020224:Expressed Sequence Tags; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D019891:Leukopoiesis; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D053655:Receptors, Interleukin-21; D013601:T-Lymphocytes / Q000276:immunology*; D014018:Tissue Distribution; D000098546:Interleukin-21
D019013:CD40 Antigens; C508117:IL21R protein, human; C508118:Il21r protein, mouse; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D008024:Ligands; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21