Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation.

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Version: author
Serval ID
serval:BIB_22C03ADD6260
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation.
Journal
The Journal of experimental medicine
Author(s)
Besseyrias V., Fiorini E., Strobl L.J., Zimber-Strobl U., Dumortier A., Koch U., Arcangeli M.L., Ezine S., Macdonald H.R., Radtke F.
ISSN
0022-1007
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
204
Number
2
Pages
331-343
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Notch1 (N1) receptor signaling is essential and sufficient for T cell development, and recently developed in vitro culture systems point to members of the Delta family as being the physiological N1 ligands. We explored the ability of Delta1 (DL1) and DL4 to induce T cell lineage commitment and/or maturation in vitro and in vivo from bone marrow (BM) precursors conditionally gene targeted for N1 and/or N2. In vitro DL1 can trigger T cell lineage commitment via either N1 or N2. N1- or N2-mediated T cell lineage commitment can also occur in the spleen after short-term BM transplantation. However, N2-DL1-mediated signaling does not allow further T cell maturation beyond the CD25(+) stage due to a lack of T cell receptor beta expression. In contrast to DL1, DL4 induces and supports T cell commitment and maturation in vitro and in vivo exclusively via specific interaction with N1. Moreover, comparative binding studies show preferential interaction of DL4 with N1, whereas binding of DL1 to N1 is weak. Interestingly, preferential N1-DL4 binding reflects reduced dependence of this interaction on Lunatic fringe, a glycosyl transferase that generally enhances the avidity of Notch receptors for Delta ligands. Collectively, our results establish a hierarchy of Notch-Delta interactions in which N1-DL4 exhibits the greatest capacity to induce and support T cell development.
Keywords
Animals, Cell Differentiation/immunology, Cell Lineage/immunology, DNA Primers, Flow Cytometry, Glycosyltransferases/metabolism, Hematopoietic Stem Cells/cytology, Membrane Proteins/metabolism, Mice, Mice, Transgenic, Protein Binding, Receptor, Notch1/metabolism, Receptor, Notch2/metabolism, Retroviridae, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/immunology, Stromal Cells, T-Lymphocytes/cytology, Transfection
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:39
Last modification date
20/08/2019 13:00
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