Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact.

Détails

ID Serval
serval:BIB_E7C8E1827B15
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
Back J., Chalifour A., Scarpellino L., Held W.
ISSN
0027-8424
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
104
Numéro
10
Pages
3978-3983
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Ly49A is an inhibitory receptor, which counteracts natural killer (NK) cell activation on the engagement with H-2D(d) (D(d)) MHC class I molecules (MHC-I) on target cells. In addition to binding D(d) on apposed membranes, Ly49A interacts with D(d) ligand expressed in the plane of the NK cells' membrane. Indeed, multivalent, soluble MHC-I ligand binds inefficiently to Ly49A unless the NK cells' D(d) complexes are destroyed. However, it is not known whether masked Ly49A remains constitutively associated with cis D(d) also during target cell interaction. Alternatively, it is possible that Ly49A has to be unmasked to significantly interact with its ligand on target cells. These two scenarios suggest distinct roles of Ly49A/D(d) cis interaction for NK cell function. Here, we show that Ly49A contributes to target cell adhesion and efficiently accumulates at synapses with D(d)-expressing target cells when NK cells themselves lack D(d). When NK cells express D(d), Ly49A no longer contributes to adhesion, and ligand-driven recruitment to the cellular contact site is strongly reduced. The destruction of D(d) complexes on NK cells, which unmasks Ly49A, is necessary and sufficient to restore Ly49A adhesive function and recruitment to the synapse. Thus, cis D(d) continuously sequesters a considerable fraction of Ly49A receptors, preventing efficient Ly49A recruitment to the synapse with D(d)+ target cells. The reduced number of Ly49A receptors that can functionally interact with D(d) on target cells explains the modest inhibitory capacity of Ly49A in D(d) NK cells. This property renders Ly49A NK cells more sensitive to react to diseased host cells.
Mots-clé
Animals, Antigens, Ly/chemistry, Antigens, Ly/genetics, Bacterial Proteins/metabolism, Cytotoxicity, Immunologic, Flow Cytometry, Genes, MHC Class I, H-2 Antigens/chemistry, Killer Cells, Natural/cytology, Ligands, Luminescent Proteins/metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Protein Binding, Receptors, Immunologic/metabolism, Synapses/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/01/2008 16:24
Dernière modification de la notice
20/08/2019 17:10
Données d'usage