Lack of intermediate‐affinity interleukin‐2 receptor in mice leads to dependence on interleukin‐2 receptor α, β and γ chain expression for T cell growth

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Abstract
An interleukin (IL)‐4 dependant mouse T cell clone 8.2 derived from an IL‐2‐dependent T cell line was characterized. As measured by flow cytometric analysis and Northern blotting, it expresses IL‐2 receptor β (IL‐2Rβ) and γ (IL‐2Rγ) chains, but has lost expression of IL‐2 receptor α chain (IL‐2Rα). To investigate the properties of the mouse IL‐2Rβγ complex and the role of IL‐2Rα gene expression, this clone was further studied. T cell clone 8.2 has lost the capacity to bind 125I‐labeled human IL‐2 under experimental conditions able to detect intermediate‐affinity IL‐2R in human cells. Mouse IL‐2 is unable to block the binding of mAb TMβ1 to 8.2 cells. Under the same experimental conditions, mouse IL‐2 blocks the binding of TMβ1 to C30‐1 cells expressing the IL‐2αβγ complex. Since TMβ1 recognizes an epitope related to the IL‐2 binding site of IL‐2Rβ, these results can be taken as a demonstration that mouse IL‐2Rβγ does not bind mouse IL‐2. Furthermore, T cell clone 8.2 does not proliferate in response to recombinant mouse or human IL‐2. On the other hand, T cell transfectant lines expressing heterospecific receptors made of the human IL‐2Rβ and mouse IL‐2Rγ chains bind 125I‐labeled human IL‐2 and proliferate in response to IL‐2. This establishes the difference between mouse and human IL‐2Rβ chains. Transfection of T cell clone 8.2 with human IL‐2Rα genes restores their capacity to proliferate in response to IL‐2. In addition, all transfectants grown in IL‐2 express the endogeneous mouse IL‐2Rα chain. When grown in IL‐4, the endogeneous mouse IL‐2Rα gene remains silent in all these transfectants. These results show that, contrary to the human, the mouse does not express an intermediate‐affinity IL‐2R. Expression of the IL‐2Rα gene is therefore required for the formation of the functional IL‐2R in mice.