Document Detail


Adhesion to target cells is disrupted by the killer cell inhibitory receptor.
MedLine Citation:
PMID:  10898979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Killer cell immunoglobulin-like receptors (KIR) inhibit the cytotoxic activity of natural killer (NK) cells by recruitment of the tyrosine phosphatase SHP-1 to immunoreceptor tyrosine-based inhibition motif (ITIM) sequences in the KIR cytoplasmic tail [1]. The precise steps in the NK activation pathway that are inhibited by KIR are yet to be defined. Here, we have studied whether the initial step of adhesion molecule LFA-1-dependent adhesion to target cells was altered by the inhibitory signal. Using stable expression of an HLA-C-specific KIR in the NK cell line YTS [2] and a two-color flow cytometry assay for conjugate formation, we show that adhesion to a target cell expressing cognate HLA-C was disrupted by KIR engagement. Conjugate formation was abruptly interrupted by KIR within less than 5 minutes. Inhibition of adhesion to target cells was mediated by a chimeric KIR molecule carrying catalytically active SHP-1 in place of its cytoplasmic tail. These results suggest that other ITIM-bearing receptors, many of which have no known function, may regulate adhesion in a wide variety of cell types.
Authors:
D N Burshtyn; J Shin; C Stebbins; E O Long
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current biology : CB     Volume:  10     ISSN:  0960-9822     ISO Abbreviation:  Curr. Biol.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-10-03     Completed Date:  2000-10-03     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  777-80     Citation Subset:  IM    
Affiliation:
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / pharmacology
Antigens, CD
Antigens, CD28 / immunology,  physiology
Antigens, Differentiation / pharmacology
CTLA-4 Antigen
Cell Adhesion / drug effects,  physiology*
Cell Line
Dose-Response Relationship, Drug
Flow Cytometry
Gene Expression
HLA-C Antigens / genetics,  physiology
Humans
Immunoconjugates*
Intracellular Signaling Peptides and Proteins
Killer Cells, Natural / cytology,  drug effects,  physiology*
Lymphocyte Function-Associated Antigen-1 / immunology,  physiology
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / genetics,  physiology
Receptors, Immunologic / genetics,  physiology*
Receptors, KIR
Recombinant Fusion Proteins / genetics,  physiology
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD; 0/Antigens, CD28; 0/Antigens, Differentiation; 0/CTLA-4 Antigen; 0/CTLA4 protein, human; 0/HLA-C Antigens; 0/HLA-C*02 antigen; 0/HLA-C*03 antigen; 0/Immunoconjugates; 0/Intracellular Signaling Peptides and Proteins; 0/Lymphocyte Function-Associated Antigen-1; 0/Receptors, Immunologic; 0/Receptors, KIR; 0/Recombinant Fusion Proteins; 7D0YB67S97/abatacept; EC 3.1.3.48/PTPN11 protein, human; EC 3.1.3.48/PTPN6 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 6; EC 3.1.3.48/Protein Tyrosine Phosphatases

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