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qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
Published on: March 6, 2019
NKG2D and Related Immunoreceptors
Roland K Strong1, Benjamin J McFarland
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Advances in Protein Chemistry
|October 27, 2004
Summary
Natural killer (NK) cells utilize NKG2D receptors to identify distressed cells. Unlike T cell receptors, NKG2D achieves broad ligand recognition through "rigid adaptation" rather than induced-fit mechanisms.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- Natural killer (NK) cells are key innate immune cells that eliminate infected or cancerous cells.
- NK cells express various activating and inhibitory receptors (NKRs), including NKG2D, which provides stimulatory signals.
- NKG2D recognizes diverse MHC class I-like ligands, indicating cellular stress from infection or transformation.
Purpose of the Study:
- To investigate the molecular mechanism behind NKG2D's degenerate ligand binding.
- To compare NKG2D's recognition mechanism with T cell receptor (TCR) cross-reactivity.
Main Methods:
- Structural analysis
- Computational modeling
- Thermodynamic and kinetic studies of NKG2D-ligand interactions.
Main Results:
- NKG2D forms 2:1 complexes with its monomeric ligands.
- NKG2D exhibits highly degenerate ligand recognition, accommodating various ligand substitutions.
- Recognition degeneracy is achieved through distinct interaction mechanisms at rigid interfaces, termed 'rigid adaptation', not classical induced-fit binding.
Conclusions:
- NKG2D employs 'rigid adaptation' for degenerate ligand recognition, a mechanism distinct from TCR's induced-fit.
- This unique binding strategy allows NKG2D to recognize a wide array of stress-induced ligands.
- Other NKG2x NKR family members may not require such extensive recognition degeneracy.
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