IL-2: Change Structure … Change Function Jeffrey A. Bluestone, Natasha Crellin, Eleonora Trotta  Immunity  Volume 42, Issue 5, Pages 779-781 (May 2015) DOI: 10.1016/j.immuni.2015.05.002 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Different Approaches to Change IL-2 Conformation to Alter Function On the left side, binding of JES6-1 to IL-2 changes the conformation of the molecule resulting in reduced IL-2Rα binding affinity. Only cells with high levels of IL-2Rα (such as Treg cells) can bind the JES6-1:IL-2 complex efficiently. The opposite function is elicited by S4B6, which increases IL-2 affinity for IL-2Rβ, resulting in effector T cell activation. The right side illustrates a different, mutational approach to generate distinct IL-2 variants, which alters IL-2R-γc binding. The affinity of the interaction between these mutants and the γc regulates signal intensity, generating IL-2 molecules that can more potently activate pSTAT5 or completely block Treg cell differentiation and induce proliferation of pre-activated CD8+ T cells. Both of these approaches generate IL-2 molecules that can function as agonists or antagonists depending on cell type. Immunity 2015 42, 779-781DOI: (10.1016/j.immuni.2015.05.002) Copyright © 2015 Elsevier Inc. Terms and Conditions