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A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity
Open accessAbstract
NK cells are involved in the immune response against viral and microbial infections and tumors. In contrast to B and T cells, NK cells employ various modes of immune recognition. An important mode of immune recognition employed by NK cells is "induced self recognition" exemplified by the NKG2D receptor–ligand system. The NKG2D immunoreceptor, expressed by NK cells, and by activated CD8+ T cells and macrophages, recognizes one of several cell surface ligands that are distantly related to MHC class I molecules (i.e. H60 and Rae1 proteins in mice, and MHC class I chain‐related proteins and UL‐16‐binding proteins in humans). These ligands are not expressed abundantly by most normal cells but are up‐regulated on cells exposed to various forms of cellular insults.Here we report the cloning of another ligand for NKG2D; transcripts of this ligand are found in a wide variety of tissues and in various tumor cells. Cross‐linking of NKG2D with the novel ligand potently activated NK cells and macrophages. Tumor cells ectopically expressing the molecule were efficiently rejected by naive mice, and induced strong protective immunity to the parental, ligand‐negative tumor cells.
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“Previous studies from our laboratory demonstrated that transplanted tumor cells expressing NKG2D ligands are rejected by NK cells and, in some cases, T cells (Diefenbach et al., 2000, 2001, 2003)”
From p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells (2013) · cites this paper as Diefenbach et al., 2003
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Metadata
- Authors
- Diefenbach, A., Hsia, J. K., Hsiung, M. B., & Raulet, D. H.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Raulet, David H.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2003-01-27
- Volume
- 33
- Issue
- 2
- Pages
- 381-391
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2090487140
- Cited by
- 170
- References
- 41
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 5 · 2013: 5 · 2012: 10
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- NKG2D, NKG2D ligands, natural killer cells, macrophages, antitumor immunity, Rae1, tumor rejection, NK cell activation
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cloning, Molecular, Cytotoxicity, Immunologic, Interferons, Killer Cells, Natural, Ligands, Macrophages, Membrane Proteins, Molecular Sequence Data, Neoplasm Transplantation, Neoplasms, Organ Specificity, Receptors, Immunologic, Recombinant Fusion Proteins, RNA, Messenger, Transfection, Transplantation, Isogeneic, Tumor Cells, Cultured, Histocompatibility Antigens Class I, Minor Histocompatibility Antigens, Lymphoma, T-Cell, Sequence Alignment, Genes, RAG-1, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Mice, Knockout, Mice, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily K
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