Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity.
Interleukin (IL-) 2 and IL-15 share the IL-2 receptor betagamma c subunits (IL-2Rbetagamma c) but have specific, unique alpha receptor subunits. We studied species specificity of human (hu), simian (si), and mouse (mu) IL-15 and found that hu and si IL-15 behaved similarly in all systems investigated. Hu and mu IL-15 bound hu or mu IL-15Ralpha with equal high affinity in the presence or absence of IL-2Rbetagamma c and exhibited similar proliferative activities on cells containing all three subunits. However, quantitative differences were noted in the specific activity of hu and mu IL-15 in both in vitro and in vivo systems utilizing IL-2Rbetagamma c in the absence of IL-15Ralpha. These data show that hu IL-15 may be used in mouse model systems, however care must be taken when comparing the efficacy and toxicity of cytokines across species.
Eisenman
June
J
Department of Protein Chemistry, Immunex Corporation, 51 University Street, Seattle, WA, 98101, USA. eisenman@immunex.com
Ahdieh
Minoo
M
Beers
Courtney
C
Brasel
Kenneth
K
Kennedy
Mary K
MK
Le
Tiep
T
Bonnert
Timothy P
TP
Paxton
Raymond J
RJ
Park
Linda S
LS
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006031:Glycosylation; D000882:Haplorhini; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2