| Autor: |
Back, Jonathan, Chalifour, Anick, Scarpellino, Leonardo, Heid, Werner |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/6/2007, Vol. 104 Issue 10, p3978-3983, 6p, 1 Diagram, 4 Graphs |
| Abstrakt: |
Ly49A is an inhibitory receptor, which counteracts natural killer (NK) cell activation on the engagement with H-2Dd (Dd) MHC class I molecules (MHC-I) on target cells. In addition to binding Dd on apposed membranes, Ly49A interacts with Dd ligand expressed in the plane of the NK cells' membrane. Indeed, multivalent, soluble MHC-I ligand binds inefficiently to Ly49A unless the NK cells' Dd complexes are destroyed. However, it is not known whether masked Ly49A remains constitutively associated with cis Dd 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/Dd cis interaction for NK cell function. Here, we show that Ly49A contributes to target cell adhesion and efficiently accumulates at synapses with Dd-expressing target cells when NK cells themselves lack Dd. When NK cells express Dd, Ly49A no longer contributes to adhesion, and ligand-driven recruitment to the cellular contact site is strongly reduced. The destruction of Dd complexes on NK cells, which unmasks Ly49A, is necessary and sufficient to restore Ly49A adhesive function and recruitment to the synapse. Thus, cis Dd continuously sequesters a considerable fraction of Ly49A receptors, preventing efficient Ly49A recruitment to the synapse with Dd+ target cells. The reduced number of Ly49A receptors that can functionally interact with Dd on target cells explains the modest inhibitory capacity of Ly49A in Dd NK cells. This property renders Ly49A NK cells more sensitive to react to diseased host cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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