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Sci Signal. 2018 Dec 18;11(561). pii: eaat0756. doi: 10.1126/scisignal.aat0756.

CD45 exclusion- and cross-linking-based receptor signaling together broaden FcεRI reactivity.

Author information

1
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
2
Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
3
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.
4
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK. simon.davis@imm.ox.ac.uk christian.eggeling@rdm.ox.ac.uk michael.dustin@kennedy.ox.ac.uk.
5
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK. simon.davis@imm.ox.ac.uk christian.eggeling@rdm.ox.ac.uk michael.dustin@kennedy.ox.ac.uk.

Abstract

For many years, the high-affinity receptor for immunoglobulin E (IgE) FcεRI, which is expressed by mast cells and basophils, has been widely held to be the exemplar of cross-linking (that is, aggregation dependent) signaling receptors. We found, however, that FcεRI signaling could occur in the presence or absence of receptor cross-linking. Using both cell and cell-free systems, we showed that FcεRI signaling was stimulated by surface-associated monovalent ligands through the passive, size-dependent exclusion of the receptor-type tyrosine phosphatase CD45 from plasma membrane regions of FcεRI-ligand engagement. Similarly to the T cell receptor, FcεRI signaling could also be initiated in a ligand-independent manner. These data suggest that a simple mechanism of CD45 exclusion-based receptor triggering could function together with cross-linking-based FcεRI signaling, broadening mast cell and basophil reactivity by enabling these cells to respond to both multivalent and surface-presented monovalent antigens. These findings also strengthen the case that a size-dependent, phosphatase exclusion-based receptor triggering mechanism might serve generally to facilitate signaling by noncatalytic immune receptors.

PMID:
30563863
DOI:
10.1126/scisignal.aat0756

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