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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Activation of Vγ9Vδ2 T Cells by NKG2D
Bladimiro Rincon-Orozco,Volker Kunzmann,Philine Wrobel,Dieter Kabelitz,Alexander Steinle,Thomas Herrmann +5 more
TL;DR: Evidence is provided that Vγ9Vδ2 T cells may also be directly activated by NKG2D, a potent costimulatory receptor in the Ag-specific activation of γδ and CD8 T cells that triggers the production of TNF-α but not of IFN-γ.
Journal ArticleDOI
UL16-Binding Proteins, Novel MHC Class I-Related Proteins, Bind to NKG2D and Activate Multiple Signaling Pathways in Primary NK Cells
Claire L. Sutherland,N. Jan Chalupny,Kenneth Schooley,Tim VandenBos,Marek Kubin,David Cosman +5 more
TL;DR: It is shown that NKG2D is the ULBP counterstructure on primary NK cells and that its expression is up-regulated by IL-15 stimulation, increasing the understanding of the mechanisms by which NKG 2D activates immune effector cells and may have implications for immune surveillance against pathogens and tumors.
Journal ArticleDOI
NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells
Jadee L. Upshaw,Laura N. Arneson,Renee A. Schoon,Christopher J. Dick,Daniel D. Billadeau,Paul J. Leibson +5 more
TL;DR: It is shown here that binding of the p85 subunit of phosphatidylinositol-3- kinase to DAP10 could not by itself trigger cell-mediated cytotoxicity and thatbinding of an intermediate consisting of the DAP 10 binding partner Grb2 and the effector molecule Vav1 to D AP10 was sufficient to initiate tyrosine-phosphorylation events.
Journal ArticleDOI
Human NK cells: surface receptors, inhibitory checkpoints, and translational applications
Simona Sivori,Paola Vacca,Genny Del Zotto,Enrico Munari,Maria Cristina Mingari,Lorenzo Moretta +5 more
TL;DR: The translational value of NK cells and their receptors is evidenced by the extraordinary therapeutic success of haploidentical HSCT to cure otherwise fatal high-risk leukemias.
Journal ArticleDOI
Surface NK receptors and their ligands on tumor cells
Lorenzo Moretta,Cristina Bottino,Daniela Pende,Roberta Castriconi,Maria Cristina Mingari,Alessandro Moretta +5 more
TL;DR: Under pathological conditions, NK cells may express insufficient amounts of triggering receptors and target cells may or may not express ligands for such receptors, leading to NK cell activation and tumor cell lysis.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.