The roles of interleukin-15 receptor alpha: trans-presentation, receptor component, or both?
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.
Schluns
Kimberly S
KS
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Stoklasek
Thomas
T
Lefrançois
Leo
L
D000818:Animals; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism*; D051379:Mice; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2