A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner.

Abstract:

:Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK) cells and a subset of T cells, recognizes stress-inducible proteins, including MICA and ULBP2, which are present on infected or transformed cells. Whether each NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Using superresolution microscopy, we found that NKG2D is constitutively arranged in nanoclusters at the surface of human primary NK cells. Nanoclusters of NKG2D became smaller upon ligation with MICA but became larger upon activation by ULBP2. In addition, ULBP2 induced the reorganization of nanoclusters of the cytokine receptor subunit for both interleukin-2 (IL-2) and IL-15 (IL-2/IL-15Rβ), such that these cytokine receptor subunits coalesced with nanoclusters of NKG2D. Functionally, the response of NK cells activated by ULBP2 was augmented by an interaction between ULBP2-bound NKG2D and IL-15R ligated by IL-15 (trans-presented by IL-15Rα-coated surfaces). These data suggest that NKG2DLs are not equivalent in their capacity to activate NKG2D and establish a previously unknown paradigm in how ligand-induced changes to the nanoscale organization of the cell surface can affect immune responses.

journal_name

Sci Signal

journal_title

Science signaling

authors

Bálint Š,Lopes FB,Davis DM

doi

10.1126/scisignal.aal3606

subject

Has Abstract

pub_date

2018-04-10 00:00:00

issue

525

eissn

1945-0877

issn

1937-9145

pii

11/525/eaal3606

journal_volume

11

pub_type

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