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Volumn 20, Issue 3, 2008, Pages 344-352

Line of attack: NK cell specificity and integration of signals

Author keywords

[No Author keywords available]

Indexed keywords

NATURAL KILLER CELL RECEPTOR;

EID: 45449115527     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2008.03.005     Document Type: Review
Times cited : (165)

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    • High sensitivity imaging of phosphorylated ITIM-containing KIR at inhibitory NK cell immune synapses has been achieved. Surprisingly, phosphorylated KIR, presumably bound to active SHP-1, is distributed in small clusters over the synapse, which does not correspond to the distribution of total KIR. These findings raise interesting questions about the mechanism of inhibition.
    • Treanor B., Lanigan P.M., Kumar S., Dunsby C., Munro I., Auksorius E., Culley F.J., Purbhoo M.A., Phillips D., Neil M.A., et al. Microclusters of inhibitory killer immunoglobulin-like receptor signaling at natural killer cell immunological synapses. J Cell Biol 174 (2006) 153-161. High sensitivity imaging of phosphorylated ITIM-containing KIR at inhibitory NK cell immune synapses has been achieved. Surprisingly, phosphorylated KIR, presumably bound to active SHP-1, is distributed in small clusters over the synapse, which does not correspond to the distribution of total KIR. These findings raise interesting questions about the mechanism of inhibition.
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    • Verbrugge A., Rijkers E.S., de Ruiter T., and Meyaard L. Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase. Eur J Immunol 36 (2006) 190-198. Inhibition by the ITIM-containing receptor LAIR-1 can occur in the absence of SHP-1, SHP-2, and SHIP binding through the recruitment of the kinase Csk. Csk mediates negative regulation of Src-family kinases by phosphorylation of their C-terminal tyrosine.
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    • Stinchcombe J.C., Majorovits E., Bossi G., Fuller S., and Griffiths G.M. Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443 (2006) 462-465. Polarization of cytotoxic granules in T cells occurs by movement of the microtubule organizing center (MTOC) toward the target cell, and centrosomes contact with the plasma membrane. Granules do not move toward the plus end of microtubules, but toward the MTOC in the minus direction.
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    • The Cdc42-interacting protein-4 (CIP4) is identified as a crucial link between actin cytoskeleton and microtubles, mediating granule polarization and cytotoxicity.
    • Banerjee P.P., Pandey R., Zheng R., Suhoski M.M., Monaco-Shawver L., and Orange J.S. Cdc42-interacting protein-4 functionally links actin and microtubule networks at the cytolytic NK cell immunological synapse. J Exp Med 204 (2007) 2305-2320. The Cdc42-interacting protein-4 (CIP4) is identified as a crucial link between actin cytoskeleton and microtubles, mediating granule polarization and cytotoxicity.
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    • •] demonstrate a role for myosin IIA in NK cell cytotoxicity. Notably, myosin IIA is required for exocytosis, but not polarization, of secretory lysosomes.
    • •] demonstrate a role for myosin IIA in NK cell cytotoxicity. Notably, myosin IIA is required for exocytosis, but not polarization, of secretory lysosomes.
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    • Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4
    • This study provides evidence for fusion of distinct vesicular compartments, which then form the secretory lysosomes that fuse with the plasma membrane for degranulation. These results challenge the notion of direct transport of secretory lysosomes to the plasma membrane for fusion.
    • Menager M.M., Menasche G., Romao M., Knapnougel P., Ho C.H., Garfa M., Raposo G., Feldmann J., Fischer A., and de Saint Basile G. Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4. Nat Immunol 8 (2007) 257-267. This study provides evidence for fusion of distinct vesicular compartments, which then form the secretory lysosomes that fuse with the plasma membrane for degranulation. These results challenge the notion of direct transport of secretory lysosomes to the plasma membrane for fusion.
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    • Mutations in syntaxin 11, a SNARE motif containing protein, cause familial hemophagocytic lymphohistiocytosis type 4, an immune disorder characterized by hyperinflammation and susceptibility to certain intracellular pathogens. These two papers show that syntaxin 11 is essential for degranulation of NK cells, thereby providing a mechanistic explanation for the disease.
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    • A potential function of KIR2DL4 in promoting neo-vascularization during early pregnancy is revealed in this study. KIR2DL4 signals for a pro-inflammatory/pro-angionenic response of resting cells from endosomes, into which it has internalized its ligand, soluble HLA-G.
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    • As previously demonstrated in mice, these results show that NK cells lacking inhibitory receptors for MHC class I are found in circulation but are functionally hyporesponsive. Together with data from animal models, these data reveal the impact of inhibitory receptor-MHC class I interactions on the potency of individual NK cells.
    • Anfossi N., Andre P., Guia S., Falk C.S., Roetynck S., Stewart C.A., Breso V., Frassati C., Reviron D., Middleton D., et al. Human NK cell education by inhibitory receptors for MHC class I. Immunity 25 (2006) 331-342. As previously demonstrated in mice, these results show that NK cells lacking inhibitory receptors for MHC class I are found in circulation but are functionally hyporesponsive. Together with data from animal models, these data reveal the impact of inhibitory receptor-MHC class I interactions on the potency of individual NK cells.
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    • Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs
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    • Dendritic cells prime natural killer cells by trans-presenting interleukin 15
    • Unexpectedly, mouse NK cells do not mount effective responses unless stimulated by dendritic cells trans-presenting IL-15. The data reveal a requirement for priming of NK cells, analogous to T cell responses.
    • Lucas M., Schachterle W., Oberle K., Aichele P., and Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26 (2007) 503-517. Unexpectedly, mouse NK cells do not mount effective responses unless stimulated by dendritic cells trans-presenting IL-15. The data reveal a requirement for priming of NK cells, analogous to T cell responses.
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