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IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells
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IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells
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Journal Article
IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells
2014
Overview
Interleukin (IL)-15 and its specific receptro chain, IL-15Rα, support the development of various effector cells, including NK and CD8 T cells via a mechanism called trans-presentation. Whereas the dynamic of trans-presentation has been shown to involve the recycling of IL-15Rα by presenting cells, the way responding cells integrate, or take advantage of this process has not been evaluated yet. To address this question, we set up a trans-presentation model using a membrane-bound IL-15.IL-15Rα fusion protein, and found that IL-15 is detectable within responding cells following IL-15 trans-presentation. The role of the proteolytic cleavage of IL-15Rα in this process was investigated by generating an uncleavable form of IL-15Rα. We showed that IL-15 entry into responding cells necessitates the cleavage of IL-15.IL-15Rα complex from the surface of IL-15 presenting cells, and observed that IL-15Rα cleavage is associated with a decrease of the duration of Stat5 signaling. Once separated from presenting cells, responding cells are able to recycle IL-15.IL-15Rα complexes via intracellular compartments, for residual proliferation in a time-limited manner. These studies define an unprecedented cytokine pathway in which the IL-15.IL-15Rα complex cleaved from presenting cells allows responding cells to internalize, store and use IL-15.IL-15Rα complex for their own proliferation and survival.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
Antigen Presentation - immunology
/ Cell Communication - immunology
/ Cells
/ Dendritic Cells - immunology
/ Dendritic Cells - metabolism
/ Humans
/ Interleukin-15 Receptor alpha Subunit - genetics
/ Interleukin-15 Receptor alpha Subunit - immunology
/ Interleukin-15 Receptor alpha Subunit - metabolism
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - metabolism
/ Protein Binding - immunology
/ Protein Transport - immunology
/ Signal Transduction - immunology
/ STAT5 Transcription Factor - immunology
