Thursday, April 19, 2012
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
(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.