Related Experiment Videos
The Qa-1b molecule binds to a large subpopulation of murine NK cells
M Salcedo1, P Bousso, H G Ljunggren
1Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris, France. msalcedo@pasteur.fr
Insights
Murine NK cells possess a structure that recognizes the nonclassical MHC class I molecule Qa-1. This finding suggests a potential Qa-1-CD94/NKG2-like complex in mice, similar to human NK cell receptors.
Area of Science:
- Immunology
- Cellular and Molecular Immunology
Background:
- Human NK (natural killer) cells utilize CD94/NKG2 receptors to bind HLA-E, a nonclassical MHC class I molecule.
- While CD94/NKG2 complexes are known in humans, their presence in rodents was unconfirmed despite cloned cDNAs for mouse and rat CD94 and NKG2.
- The mouse nonclassical MHC class I molecule Qa-1 shares characteristics with human HLA-E, suggesting it might be recognized by murine NK cells.
Purpose of the Study:
- To investigate the binding of the mouse nonclassical MHC class I molecule Qa-1 to murine NK cells.
- To determine if Qa-1 can bind to NK cells independently of other known NK cell receptors.
Main Methods:
- Production of a soluble tetrameric form of the mouse Qa-1b molecule.
- Assessment of Qa-1b tetramer binding to murine splenocytes, specifically NK1.1+/CD3- populations, using flow cytometry.
- Analysis of binding in NK cells from both MHC class I-expressing and MHC class I-deficient environments.
Main Results:
- Soluble Qa-1b tetramers demonstrated distinct binding to a significant subset of fresh and IL-2-activated murine NK1.1+/CD3- splenocytes.
- Qa-1b binding occurred independently of the expression of Ly49 inhibitory receptors on NK cells.
- Binding was observed irrespective of whether the NK cells developed in the presence or absence of MHC class I expression.
Conclusions:
- A structure capable of recognizing Qa-1 exists on a substantial subpopulation of murine NK cells.
- This Qa-1-recognizing structure may function analogously to the human CD94/NKG2 heterodimeric complex.
- The findings support the potential existence of a conserved Qa-1-CD94/NKG2-like recognition pathway in mice.
Abstract:
Recent studies on human NK cells have demonstrated that the NK cell CD94/NKG2 receptors bind to the nonclassical MHC class I molecule HLA-E. A functional CD94/NKG2 complex has not yet been identified in rodents, but cDNA encoding rat and mouse CD94 and NKG2 have recently been cloned, suggesting that CD94/NKG2 receptors may exist in species other than man. The mouse nonclassical MHC class I molecule Qa-1 shares several features with HLA-E. This suggests that Qa-1 may be similarly recognized by murine NK cells. To study the ability of Qa-1 to bind to murine NK cells, we have produced a soluble tetrameric form of Qa-1b. In the present study, we demonstrate that Qa-1b tetramers distinctly bind to a large subset of fresh or IL-2-activated NK1.1+/CD3- splenocytes independently of the expression of Ly49 inhibitory receptors. Binding occurs whether NK cells have evolved in an MHC class I-expressing or in an MHC class I-deficient environment. Our data suggest the existence of a Qa-1-recognizing structure on a large subpopulation of murine NK cells that may be similar to the human CD94/NKG2 heterodimeric complex.