IL-2 and IL-15 signaling complexes: different but the same

Ikemizu S, Chirifu M, Davis SJ (2012), Nat Immunol. 13, 1141-2

Abstract

Interleukin 2 (IL-2) and IL-15 use receptors with the same signaling subunits. New structural data show that the signaling complexes they form are topologically nearly identical, which suggests that other factors are responsible for the distinct signaling properties of these complexes.

Key figure: Signaling by IL-2 and IL-15

(a) Signaling complexes formed by IL-2 and IL-15, as determined by Ring et al.². The dotted green line indicates the possible trans presentation of IL-2 (ref. 5). Box indicates the regions of almost complete identity in both the structure and organization of the D2 domains of the signaling subunits, as now demonstrated², which position Jak1 and Jak3. (b) Different ways that identical signaling complexes could produce distinct signals in a cytotoxic T cell (T_c cell) interacting with a helper T cell (T_H cell) or macrophage. At left, despite their different architectures, the complexes have similar off rates (k_off), which results in a similar amount of phosphorylation and activation of Jak1 and Jak3 (yellow stripes). In this case, the signaling context (that is, the involvement of additional signals, such as that from the T cell antigen receptor) results in distinct signaling outcomes. At right, the two complexes have the same architecture and different off rates; as a result, engagement produces different amounts of activation of the kinases via different degrees of their phosphorylation or of their immediate substrates. (These diagrams are not intended to present the only functions of IL-2 or IL-15.)