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NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome.
- Source :
-
Blood [Blood] 2007 May 15; Vol. 109 (10), pp. 4306-12. Date of Electronic Publication: 2007 Jan 25. - Publication Year :
- 2007
-
Abstract
- Griscelli syndrome (GS) type 2 is an autosomal recessive disorder represented by pigment dilution and impaired cytotoxic T lymphocyte (CTL) activity. NK activity has been scarcely investigated in GS patients. Here, we describe a new patient, possessing a hemophagocytic syndrome with a homozygous Q118X nonsense RAB27A mutation. Single specific primer-polymerase chain reaction (SSP-PCR) was developed based on this mutation and is currently used in prenatal genetic analysis. As expected, CTLs in the patient are not functional and NK cytotoxicity against K562 or 721.221 cells is diminished. Surprisingly, however, we demonstrate that CD16-mediated killing is intact in this patient and is therefore RAB27A independent, whereas NKp30-mediated killing is impaired and is therefore RAB27A dependent. We further analyzed the signaling pathways of these 2 receptors and demonstrated phosphorylation of Vav1 after CD16 activation but not after NKp30 engagement. Thus, we identify a novel homozygous mutation in the RAB27A gene of a new GS patient, observe for the first time that some activating NK receptors function in GS patients, and demonstrate a functional dichotomy in the killing mediated by these human NK-activating receptors.
- Subjects :
- Amino Acid Sequence
Antibody-Dependent Cell Cytotoxicity genetics
Antibody-Dependent Cell Cytotoxicity immunology
Base Sequence
Cells, Cultured
DNA Mutational Analysis
Female
GPI-Linked Proteins
Humans
Infant
K562 Cells
Mutation
Natural Cytotoxicity Triggering Receptor 3
rab GTP-Binding Proteins genetics
rab27 GTP-Binding Proteins
Antigens, CD physiology
Cytotoxicity, Immunologic
Immunologic Deficiency Syndromes genetics
Immunologic Deficiency Syndromes immunology
Killer Cells, Natural immunology
Receptors, IgG physiology
Receptors, Immunologic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 109
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 17255357
- Full Text :
- https://doi.org/10.1182/blood-2006-09-047159