Killer cell inhibitory receptors: diversity, specificity, and function.

Immunological reviews ·Vol. 155 ·1997-02-00 ·Pages 135-44

Long EO, Burshtyn DN, Clark WP, Peruzzi M, Rajagopalan S, Rojo S, Wagtmann N, Winter CC

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.

MeSH Terms

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

Chemicals

Epitopes Receptors, Immunologic

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Long E O

Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA. elong@nih.gov

Burshtyn D N

Clark W P

Peruzzi M

Rajagopalan S

Rojo S

Wagtmann N

Winter C C

Article Info

Journal

Immunological reviews

Abbr.

Immunol Rev

ISSN

0105-2896

DOI

10.1111/j.1600-065x.1997.tb00946.x

elong@nih.gov

Published

1997-02-00

Pages

135-44

Language

English

Region

England

NLM ID

7702118

Subset

Databases

GENBANK

L41267, L41268, L41269, L41270, L41347, L76661, L76662, L76663, L76665, L76669, L76670, L76671, L76672, U24074, U24075, U24076, U24077, U24078, U24079, U30272, U30273, U30274, U31416, U33328, X89892, X89893, X94262, X94374, X94609, X98858

External Links

PubMed source DOI: 10.1111/j.1600-065x.1997.tb00946.x View journal details

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