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Reconstitution of functional receptor for human interleukin-2 in mouse cells

Abstract

Interleukin-2 (IL-2) has a key role in the antigen-specific clonal growth of T lymphocytes, by virtue of its interaction with a specific cell-surface receptor (IL-2R)1–4. The growth signal seems to be delivered by IL-2 bound to the high-affinity, but not the low-affinity, receptor5,6. Genes encoding IL-2 (refs 7–13) and its receptor (that is, Tac-antigen)14–17 have been cloned and analysed in detail. We have now achieved cell-type-specific reconstitution of the high-affinity human IL-2R by expressing the complementary DNA cloned from normal lymphocytes. A mouse T-lymphocytic line, EL-4, expressed human IL-2R with high (dissociation constant (Kd) = 160–220 pM) and low (Kd = 2.1–2.2 nM) affinity for recombinant human IL-2, while mouse L929 cells expressed only a single class of the IL-2R with lower affinity (Kd = 34.5 nM) for the ligand. We also show that the human IL-2R expressed in EL-4 cells responds to IL-2 and mediates reversed signal transduction: growth of the EL-4 cells harbouring the IL-2 R is inhibited specifically by human recombinant IL-2. The approach described here may provide a general experimental framework for elucidating the molecular basis of signal transduction mediated by specific receptor–ligand interaction.

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Hatakeyama, M., Minamoto, S., Uchiyama, T. et al. Reconstitution of functional receptor for human interleukin-2 in mouse cells. Nature 318, 467–470 (1985). https://doi.org/10.1038/318467a0

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