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Killer cell inhibitory receptors: diversity, specificity, and function
Author(s) -
Long Eric O.,
Burshtyn Deborah N.,
Clark William P.,
Peruzzi Marta,
Rajagopalan Sumati,
Rojo Susana,
Wagtmann Nicolai,
Winter Christine C.
Publication year - 1997
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1997.tb00946.x
Subject(s) - receptor , biology , microbiology and biotechnology , major histocompatibility complex , mhc class i , immunology , genetics , antigen
Summary: 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 o f 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 1 and delivery of a dominant negative signal to the NK cell. Functional evidence has been obtained for a role of Uie tyrosine phosphatase SHP‐1 in KIR‐mediated inhibition. The presence of a conserved molif 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.