The roles of interleukin-15 receptor alpha: trans-presentation, receptor component, or both?

Int J Biochem Cell Biol. 2005 Aug;37(8):1567-71. doi: 10.1016/j.biocel.2005.02.017. Epub 2005 Mar 5.


Interleukin-15 receptor alpha (IL-15R alpha) 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-15R alpha mediates IL-15 functions is unique among cytokines. Originally, IL-15R alpha was thought to be a component of a heterotrimeric receptor complex containing the IL-2/IL-15R beta and common gamma chains (gammaC) that were required for mediating signaling. Although IL-15R alpha may in some cases act as a component of this receptor complex, more recent evidence indicates that IL-15R alpha predominately functions by presenting IL-15 to opposing cells expressing the IL-15R betagamma signaling components. This theory is consistent with the broad, non-lymphoid expression pattern of IL-15R alpha and the evidence that IL-15R alpha 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Immunologic Memory
  • Interleukin-15 / metabolism*
  • Mice
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / chemistry
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-2 / physiology*


  • IL15RA protein, human
  • Il15ra protein, mouse
  • Interleukin-15
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2