|
Expression of functional interleukin-2 receptors in human light chain/Tac ransgenic mice Miyuki Nishi, Yasumasa Ishida & Tasuku Honjo
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606, Japan
The growth of mature T lymphocytes is regulated by interaction between interleukin-2 (IL-2) and its receptor1. Three distinct binding sites for IL-2, namely low- (Kd 10 nM), intermediate- (Kd 100 pM) and high- (Kd 10 pM) affinity sites, have been found on human and primate T lymphocytes2–4. Chemical crosslinking of labelled IL-2 to human T cells shows that two polypeptide chains, p55 (L chain) and p75 (H chain), bind IL-2 with low and intermediate affinities respectively. The high-affinity binding was shown to arise from ternary complex formation of IL-2, L and H chains5. Construction of mutants of the L-chain complementary DNA indicated that the L chain is not directly involved in growth signal transduction6. Nevertheless, expression of the IL-2 receptor L chain is tightly regulated by antigen or mitogen stimulation. To investigate the L chain function, we have produced transgenic mice using human L-chain cDNA of the IL-2 receptor under the control of a constitutive promoter. Studies on the L-chain transgenic mice showed that functionally active IL-2 receptors with high affinity were expressed on unstimulated spleen and thymus cells. The results indicate that the H chain of the IL-2 receptor is constitu-tively expressed in T cells.
References
| 1. |
Smith, K. A. A. Rev. Immun. 2, 319−333 (1984). | Article | ISI | ChemPort | |
| 2. |
Tsudo, M., Kozak, R. W., Goldman, C. K. & Waldmann, T. A. Proc. natn. Acad. Sci. U.S.A. 83, 9694−9698 (1986). | ChemPort | |
| 3. |
Teshigawara, K., Wang, H., Kato, K. & Smith, K. A. J. exp. Med. 165, 223−238 (1986). |
| 4. |
Dukovich, M. et al. Nature 327, 518−522 (1987). | Article | PubMed | ChemPort | |
| 5. |
Ogura, T. et al. Molec. biol. Med. (in the press). |
| 6. |
Kondo, S. et al. Nature 327, 64−67 (1987). | Article | PubMed | ChemPort | |
| 7. |
Nikaido, T. et al. Nature 311, 631−635 (1984). | Article | PubMed | ISI | ChemPort | |
| 8. |
Kvist, S., Robert, L. & Dobberstein, B. EMBO J. 2, 245−254 (1983). | PubMed | ISI | ChemPort | |
| 9. |
Credig, R., Lowenthal, J. W., Nabholz, M. & MacDonald, H. R. Nature 314, 98−100 (1985). | Article | PubMed | ISI | ChemPort | |
| 10. |
Raulet, D. H. Nature 314, 101−103 (1985). | Article | PubMed | ISI | ChemPort | |
| 11. |
Uchiyama, T., Broder, S. & Waldmann, T. A. J. Immun. 126, 1393−1397 (1981). | PubMed | ISI | ChemPort | |
| 12. |
Hatakeyama, M. et al. Nature 318, 467−470 (1985). | Article | PubMed | ChemPort | |
| 13. |
Kondo, S. et al. Nature 320, 75−77 (1986). | Article | PubMed | ChemPort | |
| 14. |
Lifson, J. et al. J. biol. Resp. Mod. 5, 61−72 (1986). | ChemPort | |
| 15. |
von Boehmer, H., Crisanti, A., Kisielow, P. & Haas, W. Nature 314, 539−540 (1985). | Article | PubMed | ChemPort | |
| 16. |
Lowenthal, J. W., Zubler, R. H., Nabholz, M. & MacDonald, H. R. Nature 315, 669−672 (1985). | Article | PubMed | ChemPort | |
| 17. |
Siegel, J. P., Sharon, M., Smith, P. L. & Leonard, W. J. Science 238, 75−78 (1987). | PubMed | ISI | ChemPort | |
| 18. |
Ullrich, A. et al. Nature 309, 418−425 (1984). | Article | PubMed | ISI | ChemPort | |
| 19. |
Hogan, B., Constantini, F. & Lacy, E. in Manipulating the Mouse Embryoa Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1986). |
| 20. |
Gills, S., Ferm, M. M. Ou, W. & Smith, K. A. J. Immun. 120, 2027−2032 (1978). | PubMed | ISI | ChemPort | |
| 21. |
Miyoshi, I. et al. Gann 71, 155−156 (1980). | PubMed | ISI | ChemPort | |
| 22. |
Maniatis, T., Fritsch, E. F. & Sambrook, J. in Molecular Cloning (Cold Spring Harbor Laboratory, New York, 1982). |
| 23. |
Melton, D. A. et al. Nucleic Acids Res. 12, 7035−7056 (1984). | PubMed | ISI | ChemPort | |
| 24. |
Bolton, A. E. & Hunter, W. M. Biochem. J. 133, 529−531 (1973). | PubMed | ISI | ChemPort | |
© 1988 Nature Publishing Group Privacy Policy |