Report

Molecular Editing of Cellular Responses by the High-Affinity Receptor for IgE

Science  28 Feb 2014:
Vol. 343, Issue 6174, pp. 1021-1025
DOI: 10.1126/science.1246976

You are currently viewing the abstract.

View Full Text

Allergen Affinity

Allergic responses are initiated by interaction of allergens with immunoglobulin E (IgE) antibodies, which in turn bind to IgE receptors on the surface of mast cells. Suzuki et al. (p. 1021, published online 6 February; see the Perspective by Daëron) explored how the signaling properties of such receptor complexes differ, depending on the affinity of the IgE antibody for the antigen leading to different allergic responses.

Abstract

Cellular responses elicited by cell surface receptors differ according to stimulus strength. We investigated how the high-affinity receptor for immunoglobulin E (IgE) modulates the response of mast cells to a high- or low-affinity stimulus. Both high- and low-affinity stimuli elicited similar receptor phosphorylation; however, differences were observed in receptor cluster size, mobility, distribution, and the cells’ effector responses. Low-affinity stimulation increased receptor association with the Src family kinase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2. LAT1-dependent calcium signals required for mast cell degranulation were dampened, but the role of LAT2 in chemokine production was enhanced, altering immune cell recruitment at the site of inflammation. These findings uncover how receptor discrimination of stimulus strength can be interpreted as distinct in vivo outcomes.

View Full Text