Related Experiment Videos
External and internal calibration of the MHC class I-specific receptor Ly49A on murine natural killer cells
A Kåse1, M H Johansson, M Y Olsson-Alheim
1Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Insights
Natural killer (NK) cell receptor Ly49A levels are modulated by MHC class I molecules. Both NK cell-intrinsic and extrinsic MHC class I interactions influence Ly49A expression, which can rapidly adapt in mature NK cells.
Area of Science:
- Immunology
- Cellular Immunology
- NK Cell Biology
Background:
- Murine Natural Killer (NK) cell receptor Ly49A expression is modulated by MHC class I molecules.
- NK cells from H-2Dd-transgenic mice show low Ly49A surface levels, while C57BL/6 (B6) mice exhibit high levels.
Purpose of the Study:
- To determine the distinct roles of NK cell-intrinsic vs. extrinsic MHC class I molecules in Ly49A calibration.
- To investigate if Ly49A levels are regulated in mature NK cells.
Main Methods:
- Analysis of H-2Dd/Ld transgene mosaic expression in transgenic mice.
- Adoptive transfer of spleen cells to study Ly49A regulation in mature NK cells.
Main Results:
- MHC class I molecules on surrounding cells (external ligands) down-regulate Ly49A in vivo.
- MHC class I molecules on NK cells (internal ligands) maintain low Ly49A levels post-activation in vitro.
- Receptor down-regulation of Ly49A is a rapid adaptation in mature NK cells upon H-2Dd ligand interaction.
Conclusions:
- MHC class I molecules play distinct roles as external and internal ligands in Ly49A modulation.
- Ly49A levels are not fixed and can be dynamically regulated in mature NK cells responding to environmental MHC class I changes.
Abstract:
Expression of the H-2Dd-specific inhibitory receptor Ly49A on murine NK cells is subject to MHC class I-dependent modulation in vivo. As a result, NK cells in H-2Dd-transgenic mice express low cell surface levels of Ly49A, whereas NK cells from nontransgenic C57BL/6 (B6) mice express high levels. The purpose of this study was to assess the role of MHC class I molecules on the NK cell itself vs those on surrounding cells in this calibration and to test whether the Ly49A levels are subject to regulation in mature NK cells also. Analysis of transgenic mice with mosaic expression of an H-2Dd/Ld transgene showed that MHC class I molecules on surrounding cells (external ligands) and on the NK cell itself (internal ligands) played distinct roles in the determination of Ly49A levels. External ligands were involved in down-regulation of Ly49A levels in vivo, whereas internal ligands kept the down-regulated levels of Ly49A low upon NK cell activation in vitro. Furthermore, in an experimental system based on adoptive transfer of spleen cells, receptor down-regulation of Ly49A occurred as a rapid adaptation process in mature NK cells after interaction with the H-2Dd ligand in vivo. This suggests that Ly49 levels are not fixed but can be changed in mature NK cells when they are exposed to a changed MHC class I environment.