Reconstitution of a functional IL-2 receptor by the beta-chain cDNA. A newly acquired receptor transduces negative signal.
The high-affinity IL-2R results from the noncovalent association between at least two subunits; alpha (p55) and beta (p70), both of which are capable of binding IL-2 with a low and intermediate affinity, respectively. Although the alpha-chain itself has been shown to be nonfunctional, suggestions have been made that the beta-chain mediates an IL-2 signal. To directly study the role of the beta-chain in the signal transduction, we transfected with the cDNA encoding the IL-2R beta-chain a human T lymphotropic virus-I-transformed T cell line, MT-1 originally expressing low-affinity alpha-chain alone, and established a stable transformant (designated MT-beta 7) which expressed both alpha- and beta-chains simultaneously. We showed 1) MT-beta 7 manifested the high-affinity IL-2 binding, which was completely disrupted by the anti-beta chain mAb (Mik-beta 1), 2) the 125I-IL-2 crosslinking patterns of MT-beta 7 were indistinguishable from those of cells expressing the native high-affinity IL-2R, 3) MT-beta 7, but not parental MT-1, internalized the bound IL-2 and responded to IL-2 with a negative signal, i.e., inhibition of the de novo DNA synthesis. These results clearly demonstrate that the beta-chain not only participates in forming the high-affinity IL-2R with the alpha-chain but also is directly involved in the IL-2 signal transduction.
Tsudo
M
M
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
Karasuyama
H
H
Kitamura
F
F
Nagasaka
Y
Y
Tanaka
T
T
Miyasaka
M
M
D002460:Cell Line; D003432:Cross-Linking Reagents; D004247:DNA / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D014162:Transfection
D003432:Cross-Linking Reagents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D004247:DNA