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Cutting edge: murine UL16-binding protein-like transcript 1: a newly described transcript encoding a high-affinity
Leonidas N Carayannopoulos1, Olga V Naidenko, Daved H Fremont
1Division of Pulmonary and Critical Care Medicine, Howard Hughes Medical Institute, Barnes-Jewish Hospital and Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 9, 2002
Summary
Researchers discovered a new NKG2D ligand, murine ULBP-like transcript 1 (MULT1), which is widely expressed in adult tissues. This finding expands our understanding of immune recognition and the "missing self"-response in mice.
Area of Science:
- Immunology
- Cellular and Molecular Immunology
Background:
- Murine NKG2D receptors recognize H60 and RAE1 ligands, while human NKG2D recognizes MHC class I chain-related gene (MIC) and UL16-binding protein (ULBP) ligands.
- ULBP ligands mark transformed or infected cells for NK cell destruction via the "missing self"-response.
- Murine NKG2D ligand mRNA expression is typically restricted in mature animals, unlike human counterparts.
Purpose of the Study:
- To identify and characterize novel NKG2D ligands in mice.
- To investigate the expression patterns and binding properties of a newly identified ligand.
- To assess the functional role of this ligand in natural killer (NK) cell-mediated cytotoxicity.
Main Methods:
- Description of a novel NKG2D ligand, murine ULBP-like transcript 1 (MULT1).
- Analysis of MULT1 mRNA expression in adult murine tissues.
- Biochemical characterization of MULT1 binding to NKG2D using recombinant proteins.
- Functional assays assessing the susceptibility of MULT1-expressing cells to NK cell lysis.
Main Results:
- MULT1 mRNA is widely expressed in adult murine parenchyma.
- Recombinant MULT1 binds to murine NKG2D with high affinity (K(D) ≈ 6 nM) and low dissociation rate (k(off) ≈ 0.006s⁻¹).
- Expression of MULT1 renders normally resistant RMA cells susceptible to lysis by C57BL/6 splenocytes.
Conclusions:
- MULT1 is a novel, widely expressed NKG2D ligand in mice.
- MULT1 engagement mediates NK cell cytotoxicity, potentially contributing to immune surveillance.
- This discovery provides new insights into NKG2D-mediated immune responses and the regulation of NK cell activity in mice.