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A natural killer cell receptor specific for a major histocompatibility complex class I molecule
B F Daniels1, F M Karlhofer, W E Seaman
1Department of Medicine, University of California, San Francisco.
The Journal of Experimental Medicine
|August 1, 1994
Summary
Natural killer (NK) cell receptors like Ly-49 bind to major histocompatibility complex (MHC) class I molecules on target cells. This interaction physically links NK cell Ly-49 receptors with target cell H-2Dd molecules, influencing natural killing specificity.
Area of Science:
- Immunology
- Cell Biology
- Molecular Interactions
Background:
- Major histocompatibility complex (MHC) class I expression on target cells is linked to resistance against natural killer (NK) cell lysis.
- Previous functional studies suggested the murine NK cell surface molecule Ly-49 downregulates NK cell cytotoxicity through interaction with target cell H-2Dd molecules.
Purpose of the Study:
- To demonstrate a physical interaction between the Ly-49 molecule and H-2Dd molecules.
- To investigate the role of NK cell receptors in engaging target cell MHC class I molecules.
Main Methods:
- Utilized a stable transfected Chinese hamster ovary (CHO) cell line expressing Ly-49.
- Employed MHC class I transfected target cells for cell-cell binding assays.
- Performed qualitative and quantitative binding assays and monoclonal antibody blocking experiments.
Main Results:
- Demonstrated a physical interaction between H-2Dd and Ly-49 in cell-cell binding assays.
- Binding was contingent on high-level Ly-49 expression on CHO cells and H-2Dd expression on target cells.
- Monoclonal antibody blocking confirmed the specific interaction.
Conclusions:
- NK cell receptors physically engage target cell MHC class I molecules.
- This interaction influences the specificity of natural killing.
- The findings support the hypothesis that Ly-49 binding to H-2Dd downregulates NK cell cytotoxicity.