Figure 1. IL-2 regulation of T cells. IL-2 binds and signals through a complex consisting of IL-2, IL-2 receptor a-chain (IL2-RA; CD25), IL-2 receptor b-chain (IL2-RB; CD122) and IL-2 receptor g-chain (IL2-RG; CD132).

(I) In CD25-expressing lymphocytes (such as T cells), CD25 binds to IL-2, leading to an optimized receptor-binding conformation (*) of wild-type IL-2, thus increasing the affinity of IL-2 for CD122 and CD132 and inducing efficient cell signaling and expansion. The IL-2 superkine already contains this optimized receptor-binding conformation. Because both cytokine forms interacting with the receptor complex have optimal receptor-binding conformation, the signaling in and expansion of CD25-competent cells are similar for both cytokine forms.

(II) In CD25-low T cells and NK cells, CD25 is not available to optimize the receptor-binding conformation of wild-type IL-2. Because the IL-2 superkine already contains the optimized receptor-binding conformation (*), even when CD25 is not present, the superkine binds with a higher affinity to the receptor complex and induces stronger cell signaling and expansion than wild-type IL-2. Cytotoxic T cells play a central role in antitumor and antiviral responses.