Nature 331, 267 - 269 (21 January 1988); doi:10.1038/331267a0

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- (K_d 10 nM), intermediate- (K_d 100 pM) and high- (K_d 10 pM) affinity sites, have been found on human and primate T lymphocytes^2–4. 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.

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