Killer cell inhibitory receptors: diversity, specificity, and function

Immunol Rev. 1997 Feb;155:135-44. doi: 10.1111/j.1600-065x.1997.tb00946.x.

Abstract

NK cells selectively kill target cells that fail to express self-MHC class I molecules. This selective killing results from a balance between inhibitory NK receptors specific for MHC class I molecules and activating receptors that are still largely unknown. Isolation of molecular clones for the human killer cell inhibitory receptors (KIR) revealed that KIR consist of a family of molecules with Ig ectodomains and cytoplasmic tails of varying length. Soluble complexes of KIR and HLA-C molecules established that KIR recognizes and binds to its ligand as an autonomous receptor. A functional expression system in human NK clones demonstrated that a single KIR can provide both recognition of MHC class I and delivery of a dominant negative signal to the NK cell. Functional evidence has been obtained for a role of the tyrosine phosphatase SHP-1 in KIR-mediated inhibition. The presence of a conserved motif used to recruit and activate SHP-1 in the cytoplasmic tail of KIR and of the mouse Ly-49 inhibitory receptor (otherwise structurally unrelated to KIR) represents an interesting case of evolutionary convergence. Furthermore, the motif led to the identification of other receptors with inhibitory potential, including a type I Ig-like receptor shared by mouse mast cells and NK cells.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytotoxicity, Immunologic*
  • Epitopes / immunology*
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Molecular Sequence Data
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / physiology*

Substances

  • Epitopes
  • Receptors, Immunologic

Associated data

  • GENBANK/L41267
  • GENBANK/L41268
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  • GENBANK/U24078
  • GENBANK/U24079
  • GENBANK/U30272
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  • GENBANK/U31416
  • GENBANK/U33328
  • GENBANK/X89892
  • GENBANK/X89893
  • GENBANK/X94262
  • GENBANK/X94374
  • GENBANK/X94609
  • GENBANK/X98858