Cis association of Ly49A with MHC class I restricts natural killer cell inhibition
- 15 February 2004
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 5 (3), 328-336
- https://doi.org/10.1038/ni1043
Abstract
Natural killer (NK) cell function is negatively regulated by inhibitory receptors interacting with major histocompatibility complex class I molecules expressed on target cells. Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2Dd ligand expressed on potential target cells (in trans) but also is constitutively associated with H-2Dd in cis (on the same cell). Cis association and trans interaction occur through the same binding site. Consequently, cis association restricts the number of Ly49A receptors available for binding of H-2Dd on target cells and reduces NK cell inhibition through Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells.Keywords
This publication has 48 references indexed in Scilit:
- Natural killer cell activation in mice and men: different triggers for similar weapons?Nature Immunology, 2002
- Characterization of a Murine NKT Cell Tumor Previously Described as an Acute Myelogenous LeukemiaLeukemia & Lymphoma, 2002
- Binding of the Natural Killer Cell Inhibitory Receptor Ly49A to Its Major Histocompatibility Complex Class I LigandJournal of Biological Chemistry, 2002
- H-2D Ligand Expression by Ly49A+ Natural Killer (NK) Cells Precludes Ligand Uptake from Environmental CellsThe Journal of Experimental Medicine, 2001
- Acquisition of External Major Histocompatibility Complex Class I Molecules by Natural Killer Cells Expressing Inhibitory Ly49 ReceptorsThe Journal of Experimental Medicine, 2001
- Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICAScience, 1999
- Impaired MHC class I (H-2Dd)-mediated protection against Ly-49A+ NK cells after amino acid substitutions in the antigen binding cleftEuropean Journal of Immunology, 1998
- Host MHC class I gene control of NK‐cell specificity in the mouseImmunological Reviews, 1997
- In search of the ‘missing self’: MHC molecules and NK cell recognitionImmunology Today, 1990
- Reactions and Crossreactions of a Rabbit Anti‐H2 Antigen SerumScandinavian Journal of Immunology, 1978