Spatial organization of signal transduction molecules in the NK cell immune synapses during MHC class I-regulated noncytolytic and cytolytic interactions Journal Article
| Authors: | Vyas, Y. M.; Mehta, K. M.; Morgan, M.; Maniar, H.; Butros, L.; Jung, S.; Burkhardt, J. K.; Dupont, B. |
| Article Title: | Spatial organization of signal transduction molecules in the NK cell immune synapses during MHC class I-regulated noncytolytic and cytolytic interactions |
| Abstract: | The cytolytic activity of NK cells is tightly regulated by inhibitory receptors specific for MHC class I Ags. We have investigated the composition of signal transduction molecules in the supramolecular activation clusters in the MHC class I-regulated cytolytic and noncytolytic NK cell immune synapses. KIR2DL3-positive NK clones that are specifically inhibited in their cytotoxicity by HLA-Cw*0304 and polyclonal human NK cells were used for conjugate formation with target cells that are either protected or are susceptible to NK cell-mediated cytotoxicity. Polarization of talin, microtubule-organizing center, and lysosomes occurred only during cytolytic interactions. The NK immune synapses were analyzed by three-dimensional immunofluorescence microscopy, which showed two distinctly different synaptic organizations in NK cells during cytolytic and noncytolytic interactions. The center of a cytolytic synapse with MHC class I-deficient target is comprised of a complex of signaling molecules including Src homology (SH)2-containing protein tyrosine phosphatase-1 (SHP-1). Closely related molecules with overlapping functions, such as the Syk kinases, SYK, and ZAP-70, and adaptor molecules, SH2 domain-containing leukocyte protein of 76 kDa and B cell linker protein, are expressed in activated NK cells and are all recruited to the center of the cytolytic synapse. In contrast, the noncytolytic synapse contains SHP-1, but is lacking other components of the central supramolecular activation cluster. These findings indicate a functional role for SHP-1 in both the cytolytic and noncytolytic interactions. We also demonstrate, in three-cell conjugates, that a single NK cell forms a cytolytic synapse with a susceptible target cell in the presence of both susceptible and nonsusceptible target cells. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; protein localization; protein tyrosine kinase; intracellular signaling peptides and proteins; histocompatibility antigens class i; hla-c antigens; natural killer cell; killer cells, natural; cell polarity; cytolysis; target cell; cytotoxicity, immunologic; protein-tyrosine kinases; receptor; microtubule; cell interaction; intercellular junctions; cytoskeleton; protein kinase zap 70; protein tyrosine phosphatase shp 1; zap-70 protein-tyrosine kinase; enzyme precursors; lysosome; immunofluorescence microscopy; receptors, immunologic; major histocompatibility antigen class 1; immunity, cellular; conjugation; adaptor protein; protein-tyrosine-phosphatase; protein kinase syk; talin; humans; human; priority journal; article; src homology domains; link protein |
| Journal Title: | Journal of Immunology |
| Volume: | 167 |
| Issue: | 8 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2001-10-15 |
| Start Page: | 4358 |
| End Page: | 4367 |
| Language: | English |
| PUBMED: | 11591760 |
| PROVIDER: | scopus |
| DOI: | 10.4049/jimmunol.167.8.4358 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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