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

Felce JH, Sezgin E, Wane M, Brouwer H, Dustin ML, Eggeling C, Davis SJ

Sci Signal 11 (561) - [2018-12-18; online 2018-12-18]

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.

Erdinc Sezgin

SciLifeLab Fellow

PubMed 30563863

DOI 10.1126/scisignal.aat0756

Crossref 10.1126/scisignal.aat0756

pii: 11/561/eaat0756

Publications 9.5.0