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Ancient interleukins 2, 15, and 15-like exhibited distinct functions but all bound IL-15Ra

Eureka Alert

IMAGE: The related cytokines IL-15, IL-15L, and IL-2 bind to receptor chain IL-15Rα or, in the case of mammalian IL-2, to IL-2Rα, and have distinct functions…. view more 

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Credit: Johannes M. Dijkstra


The cytokine family including interleukin-2 and -15 (IL-2 and IL-15) started out in a primitive vertebrate species with three related cytokines IL-2, IL-15, and IL-15-like (IL-15L), all sharing binding capacity for receptor chain IL-15Rα. IL-15L was conserved in fishes, reptiles, and some mammals but lost in human and mouse. Researchers in Japan, Germany, and the UK, have now determined the function of IL-15L using rainbow trout. Data suggest that in the jawed vertebrate ancestor IL-15 and IL-15L, forming “heterodimer cytokine” complexes with IL-15Rα, selectively induced type 1 (aka Th1) and type 2 (aka Th2) immunity, respectively, whereas free IL-2 efficiently stimulated activated and regulatory T cells by binding their surface IL-15Rα. Insights into their evolution should inspire further studies of human IL-2 and IL-15, both of which are used or tested in cancer immunotherapy.


In human and mouse, the closely related cytokines IL-2 and IL-15 both signal through IL-2Rβ heterodimer receptors, and also bind to a third receptor chain of a different molecular family, cytokine-specific IL-2Rα or IL-15Rα, which has no


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