Journal article
CD45 exclusion and crosslinking-based receptor signaling together broaden FcεRI reactivity
- 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 crosslinking. 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 crosslinking-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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 92.1MB, Terms of use)
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- Publisher copy:
- 10.1126/scisignal.aat0756
Authors
+ Wellcome Trust
More from this funder
- Funding agency for:
- Felce, J
- Dustin, M
- Eggeling, C
- Davis, S
- Grant:
- 107375/Z/15/Z
- 100262/Z/12/Z
- 104924/14/Z/14
- 098274/Z/12/Z
- 091911
- Publisher:
- American Association for the Advancement of Science
- Journal:
- Science Signaling More from this journal
- Volume:
- 11
- Issue:
- 561
- Pages:
- eaat0756
- Publication date:
- 2018-12-18
- Acceptance date:
- 2018-11-30
- DOI:
- ISSN:
-
1937-9145 and 1945-0877
- Pubs id:
-
pubs:949401
- UUID:
-
uuid:2b046971-f83b-4700-83d1-be6df3808f0c
- Local pid:
-
pubs:949401
- Source identifiers:
-
949401
- Deposit date:
-
2018-12-03
Terms of use
- Copyright holder:
- Felce et al
- Copyright date:
- 2018
- Notes:
- Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuse This is an article distributed under the terms of the Science Journals Default License. This is the accepted manuscript version of the article. The final version is available online from American Association for the Advancement of Science at: https://doi.org/10.1126/scisignal.aat0756
- Licence:
- Other
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