Killer cell inhibitory receptors: diversity, specificity, and function.
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.
Long
E O
EO
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA. elong@nih.gov
Burshtyn
D N
DN
Clark
W P
WP
Peruzzi
M
M
Rajagopalan
S
S
Rojo
S
S
Wagtmann
N
N
Winter
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000502:physiology*
D000939:Epitopes; D011971:Receptors, Immunologic