Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 2, Pages 516-527Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200636693
Keywords
cis interaction; immune synapse; Ly49; MHC class I; NK cell
Categories
Funding
- MRC [G0500563] Funding Source: UKRI
- Medical Research Council [G1001044, G0500563] Funding Source: Medline
- Medical Research Council [G0500563] Funding Source: researchfish
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Murine natural killer (NK) cells are inhibited by target cell MHC class I molecules via Ly49 receptors. However, Ly49 receptors can be made inaccessible to target cell MHC class I by a cis interaction with its MHC class I ligand within the NK cell membrane. it has recently been demonstrated that MHC class I proteins transfer from the target cells to the NK cell. Here, we establish that the number of transferred MHC class I proteins is proportional to the number of Ly49A receptors at the NK cell surface. Ly49A(+) NK cells from mice expressing the Ly49A ligand H-2D(d) showed a 90% reduction in Ly49A accessibility compared to Ly49A(+) NK cells from H-2D(d)-negative mice. The reduction was caused both by lower expression of Ly49A and interactions in cis between Ly49A and H-2D(d) at the NK cell surface. Approximately 75% of the Ly49A receptors on H-2D(d)- expressing NK cells were occupied in cis with endogenous H-2D(d) and only 25% were free to interact with H-2D(d) molecules in trans. Thus, H-2D(d) ligands control Ly49A receptor accessibility through interactions both in cis and in trans.
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