Journal ArticleDOI
Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA
Stefan Bauer,Veronika Groh,Jun Wu,Alexander Steinle,Joseph H. Phillips,Lewis L. Lanier,Thomas Spies +6 more
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TLDR
An activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses is defined.Abstract:
Stress-inducible MICA, a distant homolog of major histocompatibility complex (MHC) class I, functions as an antigen for gammadelta T cells and is frequently expressed in epithelial tumors. A receptor for MICA was detected on most gammadelta T cells, CD8+ alphabeta T cells, and natural killer (NK) cells and was identified as NKG2D. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gammadelta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses.read more
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Natural killer cells: role in local tumor growth and metastasis
TL;DR: NK cell mechanisms to kill cancer cells, their role in host immune responses against tumor growth or metastasis, and their implications in antitumor immunotherapies via cytokines, antibodies, or in combination with other therapies are summarized.
Journal ArticleDOI
Chemotherapy and zoledronate sensitize solid tumour cells to Vgamma9Vdelta2 T cell cytotoxicity.
TL;DR: In this paper, the authors demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate.
Journal ArticleDOI
Immune recognition and rejection of allogeneic skin grafts
TL;DR: Several studies demonstrate that NK cells, activated due to missing self-MHC class I molecules on allogeneic cells, are involved in allogeneIC skin graft rejection via direct killing of donor cells and through the production of proinflammatory cytokines including IFN-γ and TNF-α.
Journal ArticleDOI
IL-21 Enhances Tumor Rejection through a NKG2D-Dependent Mechanism
Rayna Takaki,Yoshihiro Hayakawa,Andrew J. Nelson,Pallavur V. Sivakumar,Steven J. Hughes,Mark J. Smyth,Lewis L. Lanier +6 more
TL;DR: IL-21 therapy may work optimally against tumors that can elicit a NKG2D-mediated immune response and is observed to enhance RMA-retinoic acid early inducible-1δ tumor rejection in RAG-1−/− deficient mice, demonstrating that the IL-21-induced protective effect can be mediated by the innate immune system and that, in this case, IL- 21 does not require the adaptive immune response.
Journal ArticleDOI
Syk Regulation of Phosphoinositide 3-Kinase-Dependent NK Cell Function
Kun Jiang,Bin Zhong,Danielle L. Gilvary,Brian C. Corliss,Eric Vivier,Elizabeth Hong-Geller,Sheng Wei,Julie Y. Djeu +7 more
TL;DR: Inhibition of Syk function by kinase-deficient Syk or piceatannol blocked target cell-induced PI3K, Rac1, PAK1, mitogen-activated protein/ERK kinase, and ERK activation, perforin movement, as well as NK cytotoxicity, indicating that Syk is upstream of all these signaling events.
References
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Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy
TL;DR: It is shown that murine lymphoma cells selected for loss of H–2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive.
Journal ArticleDOI
HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C
Veronique M. Braud,David S.J. Allan,Christopher A. O’Callaghan,Kalle Söderström,Annalisa D'Andrea,Graham S. Ogg,Sasha Lazetic,Neil Thomas Young,John I. Bell,Joseph H. Phillips,Lewis L. Lanier,Andrew J. McMichael +11 more
TL;DR: The identification of ligands for HLA-E is reported, which shows that a subset of HLA class I alleles has been shown to inhibit killing by CD94/NKG2A+ NK-cell clones, and only the HLA alleles that possess a leader peptide capable of upregulating Hla-E surface expression confer resistance toNK-cell-mediated lysis.
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Nk cell receptors
TL;DR: Three distinct receptor families, Ly49, CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class I molecules and a common pathway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these otherwise structurally diverse receptors.
Journal ArticleDOI
Cloning the differences between two complex genomes.
TL;DR: The analysis of the differences between two complex genomes holds promise for the discovery of infectious agents and probes useful for genetic studies, and may also be used for isolating probes linked to sites of genomic rearrangements.
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Recognition of Stress-Induced MHC Molecules by Intestinal Epithelial γδ T Cells
TL;DR: In this paper, the expression and recognition of a major histocompatibility complex (MHC) class I-related molecule, MICA, matches this localization, and the closely related MICB were recognized by intestinal epithelial T cells expressing diverse Vδ1 γδ TCRs.