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qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
Published on: March 6, 2019
Killer cell inhibitory receptors: diversity, specificity, and function
E O Long1, D N Burshtyn, W P Clark
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA. elong@nih.gov
Immunological Reviews
|February 1, 1997
Summary
Natural killer (NK) cells use killer cell inhibitory receptors (KIR) to recognize target cells. KIR binding to MHC class I molecules delivers an inhibitory signal, preventing NK cell activation and promoting self-tolerance.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- Natural killer (NK) cells are crucial for innate immunity, selectively eliminating target cells lacking self-major histocompatibility complex (MHC) class I molecules.
- NK cell-mediated cytotoxicity is regulated by a balance between activating and inhibitory receptors, with inhibitory receptors recognizing MHC class I molecules.
Purpose of the Study:
- To investigate the molecular mechanisms underlying killer cell inhibitory receptor (KIR) function in NK cell-mediated cytotoxicity.
- To elucidate the role of SHP-1 tyrosine phosphatase in KIR-mediated inhibition and explore evolutionary convergence in inhibitory receptor signaling.
Main Methods:
- Isolation and characterization of molecular clones for human killer cell inhibitory receptors (KIR).
- Formation of soluble KIR-HLA-C complexes to study ligand binding.
- Functional expression systems in human NK clones to assess KIR-mediated signaling.
- Analysis of conserved motifs for SHP-1 recruitment and activation.
Main Results:
- KIR molecules, comprising a family with varying Ig ectodomains and cytoplasmic tails, recognize and bind HLA-C molecules as autonomous receptors.
- A single KIR can mediate both MHC class I recognition and deliver a dominant negative signal to NK cells.
- Functional evidence implicates SHP-1 tyrosine phosphatase in KIR-mediated inhibition.
- A conserved motif for SHP-1 recruitment in KIR and mouse Ly-49 receptors suggests evolutionary convergence, leading to the identification of other inhibitory receptors.
Conclusions:
- KIR receptors play a critical role in NK cell self-recognition and inhibition through direct interaction with MHC class I molecules.
- SHP-1 is a key mediator of KIR-induced NK cell inhibition, highlighting a conserved signaling pathway.
- The identification of a conserved inhibitory motif expands our understanding of immune receptor regulation and evolutionary adaptation.
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