Journal article
Initiation of T cell signaling by CD45 segregation at 'close contacts'
- Abstract:
- It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Accepted manuscript, pdf, 5.5MB, Terms of use)
-
(Figures/images, zip, 174.2MB, Terms of use)
-
- Publisher copy:
- 10.1038/ni.3392
Authors
+ Medical Research Council
More from this funder
- Grant:
- G0700232
- G0700232
- Funding agency for:
- Aricescu, AR
+ Wellcome Trust
More from this funder
- Funding agency for:
- Davis, SJ
- Gilbert, RJC
- Grant:
- 098274/Z/12/Z
- 090532/Z/09/Z
- 098274/Z/12/Z
- 090708/Z/09/Z
- 090532/Z/09/Z
- 090532/Z/09/Z
- 060208/Z/00/Z
- 098274/Z/12/Z
+ Cancer Research UK
More from this funder
- Funding agency for:
- Jones, EY
- Grant:
- C375/A10976
- C20724/A14414
- C375/A10976
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Immunology More from this journal
- Volume:
- 17
- Issue:
- 5
- Pages:
- 574–582
- Publication date:
- 2016-03-21
- Acceptance date:
- 2015-12-29
- DOI:
- EISSN:
-
1529-2916
- ISSN:
-
1529-2908
- Language:
-
English
- Pubs id:
-
pubs:610140
- UUID:
-
uuid:f3fe8fb7-dad9-4b9b-9f35-08621d56cae7
- Local pid:
-
pubs:610140
- Source identifiers:
-
610140
- Deposit date:
-
2016-03-15
Terms of use
- Copyright holder:
- Nature America, Inc.
- Copyright date:
- 2016
- Rights statement:
- © 2016 Nature America, Inc. All rights reserved.
- Notes:
- This is the accepted manuscript version of the article. The final version is available online from Nature Publishing Group at https://dx.doi.org/10.1038/ni.3392
If you are the owner of this record, you can report an update to it here: Report update to this record