Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice.
The growth of mature T lymphocytes is regulated by interaction between interleukin-2 (IL-2) and its receptor. 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 lymphocytes. 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 chains. Construction of mutants of the L-chain complementary DNA indicated that the L chain is not directly involved in growth signal transduction. 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 constitutively expressed in T cells.
Nishi
M
M
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Ishida
Y
Y
Honjo
T
T
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013154:Spleen / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000032:analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D004247:DNA