The roles of interleukin-15 receptor α: Trans-presentation, receptor component, or both?

Interleukin-15 receptor α (IL-15Rα) is a high affinity IL-15 binding protein that is crucial for mediating IL-15 functions such as memory CD8 T cell proliferation and NK, NK/T cell, and intestinal intraepithelial lymphocyte development. However, the mechanism by which IL-15Rα mediates IL-15 functions is unique among cytokines. Originally, IL-15Rα was thought to be a component of a heterotrimeric receptor complex containing the IL-2/IL-15Rβ and common γ chains (γC) that were required for mediating signaling. Although IL-15Rα may in some cases act as a component of this receptor complex, more recent evidence indicates that IL-15Rα predominately functions by presenting IL-15 to opposing cells expressing the IL-15Rβγ signaling components. This theory is consistent with the broad, non-lymphoid expression pattern of IL-15Rα and the evidence that IL-15Rα expression by lymphocytes is dispensable for IL-15 action in vivo. This new concept of cytokine delivery will allow us to better understand the regulation and function IL-15.