| First Author | Mortier E | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 5 | Pages | 1213-25 |
| PubMed ID | 18458113 | Mgi Jnum | J:136221 |
| Mgi Id | MGI:3795645 | Doi | 10.1084/jem.20071913 |
| Citation | Mortier E, et al. (2008) IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 205(5):1213-25 |
| abstractText | Natural killer (NK) cells are innate immune effectors that mediate rapid responses to viral antigens. Interleukin (IL)-15 and its high affinity IL-15 receptor, IL-15Ralpha, support NK cell homeostasis in resting animals via a novel trans presentation mechanism. To better understand how IL-15 and IL-15Ralpha support NK cell activation during immune responses, we have used sensitive assays for detecting native IL-15 and IL-15Ralpha proteins and developed an assay for detecting complexes of these proteins. We find that IL-15 and IL-15Ralpha are preassembled in complexes within the endoplasmic reticulum/Golgi of stimulated dendritic cells (DCs) before being released from cells. IL-15Ralpha is required for IL-15 production by DCs, and IL-15 that emerges onto the cell surface of matured DCs does not bind to neighboring cells expressing IL-15Ralpha. We also find that soluble IL-15-IL-15Ralpha complexes are induced during inflammation, but membrane-bound IL-15-IL-15Ralpha complexes, rather than soluble complexes, support NK cell activation in vitro and in vivo. Finally, we provide in vivo evidence that expression of IL-15Ralpha specifically on DCs is critical for trans presenting IL-15 and activating NK cells. These studies define an unprecedented cytokine-receptor biosynthetic pathway in which IL-15Ralpha serves as a chaperone for IL-15, after which membrane-bound IL-15Ralpha-IL-15 complexes activate NK cells via direct cell-cell contact. |
