Ligand dimensions are important in controlling NK-cell responses
| Autor: | Friedemann Gebhardt, Jian-Guo Chai, Joanna Brzostek, Rui Zhao, P. Anton van der Merwe, Keith G. Gould, Dirk H. Busch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cytotoxicity
Immunologic NK Cell Lectin-Like Receptor Subfamily K Lymphocyte Immunology Cell CHO Cells Biology Ligands NK-cell ligands Minor Histocompatibility Antigens Cellular activation 03 medical and health sciences Mice 0302 clinical medicine Cricetulus Cell Line Tumor Cricetinae medicine Immunology and Allergy Animals Transgenes Receptor 030304 developmental biology 0303 health sciences Ligand Chinese hamster ovary cell H-2 Antigens Cell surface molecules NK cells NKG2D Cell biology Killer Cells Natural Mice Inbred C57BL Mutagenesis Insertional medicine.anatomical_structure Cell culture Mutagenesis Site-Directed NK Cell Lectin-Like Receptor Subfamily A 030215 immunology Protein Binding Molecular Immunology |
| Zdroj: | European Journal of Immunology |
| Popis: | Size-dependent protein segregation at the cell-cell contact interface has been suggested to be critical for regulation of lymphocyte function. We investigated the role of ligand dimensions in regulation of mouse NK-cell activation and inhibition. Elongated forms of H60a, a mouse NKG2D ligand, were generated and expressed stably in the RMA cell line. RMA cells expressing the normal size H60a were lysed efficiently by both freshly isolated and IL-2 stimulated C57BL/6 mouse-derived NK cells; however the level of lysis decreased as the H60a ligand size increased. Importantly, H60a elongation did not affect NKG2D binding, as determined by soluble NKG2D tetramer staining, and by examining NK-cell target cell conjugate formation. CHO cells are efficient at activating NK cells from C57BL/6 mice, and expression of a single chain form of H-2K(b), a ligand for the mouse inhibitory receptor Ly49C, strongly inhibited such activation of Ly49C/I positive NK cells. Elongation of H-2K(b) resulted in decreased inhibition of both lysis and IFN-gamma production by NK cells. These results establish that small ligand dimensions are important for both NK-cell activation and inhibition, and suggest that there are shared features between the mechanisms of receptor triggering on different types of lymphocytes. |
| Databáze: | OpenAIRE |
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