Signaling from immunotyrosine-based inhibitory motifs (ITIMs) neutralizes activating signals by inducing a retraction of NK cells from the surface of stimulatory cells

Abram

Arana

Atwal

Barber

Billadeau

Binstadt

Bléry

Boyington

Bruhns

Bryceson

Bunnell

Burshtyn

Bustelo

Campi

Culley

Davis

Decot

Endt

Eriksson

Ernesto Merino

Esser

Faure

Galandrini

Garboczi

Guerra

Harwood

Kaufman

Krzewski

Lanier

Lewis

Lillemeier

Long

Masilamani

Morgan Huse

Mossman

Nolz

Olcese

Orange

Ostergaard

Peterson

Quann

Riedl

Riteau

Robertson

Small

Stebbins

Stinchcombe

Swat

Takayama

Thushara P. Abeyweera

Treanor

Valiante

Varma

Veldhuyzen

Vyas

Watzl

Yokosuka

English

PubMed

Natural killer (NK) lymphocytes use a variety of activating receptors to recognize and kill infected or tumorigenic cells during an innate immune response. To prevent targeting healthy tissue, NK cells also express numerous inhibitory receptors that signal through immunotyrosine-based inhibitory motifs (ITIMs). Precisely how signals from competing activating and inhibitory receptors are integrated and resolved is not understood. To investigate how ITIM receptor signaling impinges on activating pathways, we developed a photochemical approach for stimulating the inhibitory receptor KIR2DL2 during ongoing NK cell–activating responses in high-resolution imaging experiments. Photostimulation of KIR2DL2 induces the rapid formation of inhibitory receptor microclusters in the plasma membrane and the simultaneous suppression of microclusters containing activating receptors. This is followed by the collapse of the peripheral actin cytoskeleton and retraction of the NK cell from the source of inhibitory stimulation. These results suggest a cell biological basis for ITIM receptor signaling and establish an experimental framework for analyzing it.</jats:p

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The Journal of Cell Biology

Inhibitory signaling blocks activating receptor clustering and induces cytoskeletal retraction in natural killer cells

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3044118

Inhibitory signaling blocks activating receptor clustering and induces cytoskeletal retraction in natural killer cells

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