Analysis of dynamics and functions of high-affinity interleukin-2 receptors.

Activated T cells express at least two affinity classes of interleukin-2 (IL-2) receptors. The number of low-affinity receptors is normally 10-30 times greater than that of the high-affinity receptors. In this report, normal human T cells are used in a cellular system in which the number of low-affinity receptors can be manipulated. The resulting receptor composition, which has been characterized in a previous report, contain such decreased levels of low-affinity IL-2 receptors that almost half of the surface pool of anti-IL-2 receptor antibody (anti-Tac) binding sites is associated with high-affinity receptors. By using such cells the dynamics and functions of high-affinity IL-2 receptors were studied and compared with receptors on a cell population expressing the normal 10-30-fold excess of anti-Tac binding sites over high-affinity IL-2 receptors. The results reveal that the rapid turnover of high-affinity IL-2 receptors is independent of the quantitative level of Tac antigen expression. The rapid kinetic of IL-2 internalization results in a 80-90% reduction of the steady-state levels of high-affinity receptors in the presence of IL-2. Most importantly, by using a cell population that expresses very low levels of Tac antigens, it became evident that IL-2 internalization is associated with an immediate substantial decrease of the surface level of anti-Tac binding sites. The Tac antigen thus appeared to be internalized together with the high-affinity IL-2 receptor complex but nevertheless the normal 10-30-fold excess of Tac antigens, over high-affinity IL-2 receptors, seems not to influence the process of internalization.