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NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis.
- Source :
-
The Journal of experimental medicine [J Exp Med] 1998 Jun 15; Vol. 187 (12), pp. 2065-72. - Publication Year :
- 1998
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Abstract
- After culture in interleukin (IL)-2, natural killer (NK) cells acquire an increased capability of mediating non-major histocompatibility complex (MHC)-restricted tumor cell lysis. This may reflect, at least in part, the de novo expression by NK cells of triggering receptors involved in cytolysis. In this study we identified a novel 44-kD surface molecule (NKp44) that is absent in freshly isolated peripheral blood lymphocytes but is progressively expressed by all NK cells in vitro after culture in IL-2. Different from other markers of cell activation such as CD69 or VLA.2, NKp44 is absent in activated T lymphocytes or T cell clones. Since NKp44 was not detected in any of the other cell lineages analyzed, it appears as the first marker specific for activated human NK cells. Monoclonal antibody (mAb)-mediated cross-linking of NKp44 in cloned NK cells resulted in strong activation of target cell lysis in a redirected killing assay. This data indicated that NKp44 can mediate triggering of NK cell cytotoxicity. mAb-mediated masking of NKp44 resulted in partial inhibition of cytolytic activity against certain (FcgammaR-negative) NK-susceptible target cells. This inhibition was greatly increased by the simultaneous masking of p46, another recently identified NK-specific triggering surface molecule. These data strongly suggest that NKp44 functions as a triggering receptor selectively expressed by activated NK cells that, together with p46, may be involved in the process of non-MHC-restricted lysis. Finally, we show that p46 and NKp44 are coupled to the intracytoplasmic transduction machinery via the association with CD3zeta or KARAP/DAP12, respectively; these associated molecules are tyrosine phosphorylated upon NK cell stimulation.
- Subjects :
- Biomarkers
Cells, Cultured
Flow Cytometry
Humans
Interleukin-2 pharmacology
Killer Cells, Natural drug effects
Natural Cytotoxicity Triggering Receptor 1
Natural Cytotoxicity Triggering Receptor 2
Receptors, Immunologic immunology
Signal Transduction
Cytotoxicity, Immunologic
Killer Cells, Natural immunology
Minor Histocompatibility Antigens immunology
Receptors, Immunologic isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 187
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 9625766
- Full Text :
- https://doi.org/10.1084/jem.187.12.2065