Research Topics
Genomes and Genes
| Eric O LongSummaryAffiliation: National Institutes of Health Country: USA Publications
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Detail Information
Publications
Controlling natural killer cell responses: integration of signals for activation and inhibitionEric O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Annu Rev Immunol 31:227-58. 2013..These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness...
Ready for prime time: NK cell priming by dendritic cellsEric O Long
Laboratory of Immunogenetics, NIAID NIH, 12441 Parklawn Drive, Rockville, MD 20852, USA
Immunity 26:385-7. 2007..In this issue of Immunity, Lucas et al. (2007) repeal this view by showing that NK cells acquire functionality through priming by dendritic cells...
Stress signals activate natural killer cellsEric O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA
J Exp Med 196:1399-402. 2002
Negative signaling by inhibitory receptors: the NK cell paradigmEric O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Immunol Rev 224:70-84. 2008..Advances in our understanding of the molecular details of inhibitory signaling in NK cells have provided a conceptual framework to address how ITIM-mediated regulation controls cellular reactivity in diverse cell types...
Tumor cell recognition by natural killer cellsEric O Long
Laboratory of Immunogenetics, NIAID, NIH, Rockville, MD 20852, USA
Semin Cancer Biol 12:57-61. 2002..Several activation receptors on NK cells have been identified that contribute to tumor cell recognition. One such receptor, NKG2D, is expressed by all NK cells and binds to inducible ligands on tumor cells...
Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158)E O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Immunol Rev 181:223-33. 2001..As the receptors and the signaling pathways that induce NK cytotoxicity are not fully characterized, elucidation of the inhibitory mechanism employed by KIR may provide insight into NK activation...
Natural killer cell receptorsE O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland, 20852, USA
Curr Opin Immunol 9:344-50. 1997..Mouse natural killer cells recognize MHC class I molecules through the C-type lectin Ly49 receptors but also express a receptor, of unknown ligand specificity, that is related to the killer cell inhibitory receptor...
Regulation of immune responses through inhibitory receptorsE O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Annu Rev Immunol 17:875-904. 1999..Ligands for many of the other receptors have yet to be identified. The inhibitory-receptor superfamily appears to regulate many types of immune responses by blocking cellular activation signals...
Killer cell inhibitory receptors: diversity, specificity, and functionE O Long
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA
Immunol Rev 155:135-44. 1997..Furthermore, the motif led to the identification of other receptors with inhibitory potential, including a type I Ig-like receptor shared by mouse mast cells and NK cells...
Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cellsYenan T Bryceson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Exp Med 202:1001-12. 2005..These data show that cytotoxicity by resting NK cells is controlled tightly by separate or cooperative signals from different receptors for granule polarization and degranulation...
Vav1 dephosphorylation by the tyrosine phosphatase SHP-1 as a mechanism for inhibition of cellular cytotoxicityChristopher C Stebbins
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Mol Cell Biol 23:6291-9. 2003..Such a mechanism explains how inhibitory receptors can block activating signals induced by different receptors...
LFA-1 contributes an early signal for NK cell cytotoxicityDomingo F Barber
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 173:3653-9. 2004..Thus, in contrast to T cells, in which even adhesion through LFA-1 is dependent on signals from other receptors, NK cells receive early activation signals directly through LFA-1...
Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligaseHun Sik Kim
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD 20852, USA
Immunity 32:175-86. 2010..Therefore, NK cell activation by synergizing receptors is regulated at the level of Vav1 by a hierarchy of inhibitory mechanisms...
Tethering of intercellular adhesion molecule on target cells is required for LFA-1-dependent NK cell adhesion and granule polarizationCatharina C Gross
Molecular and Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 185:2918-26. 2010..Our findings suggest that the lateral diffusion of integrin ligands on cells may be an important determinant of susceptibility to lysis by cytotoxic lymphocytes...
β2 integrin induces TCRζ-Syk-phospholipase C-γ phosphorylation and paxillin-dependent granule polarization in human NK cellsMichael E March
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
J Immunol 186:2998-3005. 2011..Therefore, common signals triggered by CD16 and LFA-1 bifurcate to provide independent control of Ca(2+)-dependent degranulation and paxillin-dependent granule polarization...
Lytic granule polarization, rather than degranulation, is the preferred target of inhibitory receptors in NK cellsAsmita Das
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 185:4698-704. 2010..Therefore, granule polarization, rather than degranulation, is the preferred target of inhibitory receptors in NK cells...
Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapsesDongfang Liu
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Immunity 31:99-109. 2009..Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling...
Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cellsHun Sik Kim
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Sci Signal 5:ra49. 2012..Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation...
Vav1 phosphorylation is induced by beta2 integrin engagement on natural killer cells upstream of actin cytoskeleton and lipid raft reorganizationBeatrice Riteau
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Exp Med 198:469-74. 2003..Therefore, binding of LFA-1 to ICAM-1 on target cells may initiate an early signaling cascade in NK cells through activation of Vav1, leading to cytoskeleton reorganization and amplification of signals from other activation receptors...
Cutting edge: NKG2D-dependent cytotoxicity is controlled by ligand distribution in the target cell membraneEmily Martinez
Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 186:5538-42. 2011..These results show that the partitioning of receptor ligands in discrete membrane domains of target cells is an important determinant of NK cell activation...
Spontaneous clustering and tyrosine phosphorylation of NK cell inhibitory receptor induced by ligand bindingMathias Faure
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA
J Immunol 170:6107-14. 2003..The unique property of KIR to become phosphorylated in the absence of adhesion and of actin cytoskeleton rearrangement explains how KIR can efficiently block early activation signals during NK-target cell contacts...
Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptorsYenan T Bryceson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health NIH, Rockville, MD 20852, USA
Blood 114:2657-66. 2009..These results reveal multiple layers in the activation pathway for natural cytotoxicity and that steps as distinct as inside-out signaling to LFA-1 and signals for granule release are sensitive to inhibition by CD94/NKG2A...
DNA-PKcs controls an endosomal signaling pathway for a proinflammatory response by natural killer cellsSumati Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Sci Signal 3:ra14. 2010..The sequential requirement for DNA-PKcs, Akt, and NF-kappaB in signaling by CD158d delineates a previously uncharacterized endosomal signaling pathway for a proinflammatory response in NK cells...
Use of transfected Drosophila S2 cells to study NK cell activationMichael E March
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA
Methods Mol Biol 612:67-88. 2010..Here, we present methods for maintenance and transfection of S2 cells, as well as protocols for their use in NK cell assays...
The adaptor protein Crk controls activation and inhibition of natural killer cellsDongfang Liu
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Immunity 36:600-11. 2012....
Inhibitory receptor signaling via tyrosine phosphorylation of the adaptor CrkMary E Peterson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Immunity 29:578-88. 2008....
Recruitment of activation receptors at inhibitory NK cell immune synapsesNicolas Schleinitz
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, USA
PLoS ONE 3:e3278. 2008..These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses...
Activation of NK cells by an endocytosed receptor for soluble HLA-GSumati Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA
PLoS Biol 4:e9. 2006....
Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretionYenan T Bryceson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, 12441 Parklawn Dr, Rockville, MD 20852, USA
Blood 107:159-66. 2006..Therefore, natural cytotoxicity by resting NK cells is induced only by mutual costimulation of nonactivating receptors. These results reveal distinct and specific patterns of synergy among receptors on resting NK cells...
Natural killer cell inhibitory receptors block actin cytoskeleton-dependent recruitment of 2B4 (CD244) to lipid raftsCarsten Watzl
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Exp Med 197:77-85. 2003..Blocking actin cytoskeleton-dependent raft recruitment of different receptors may be a general mechanism by which inhibitory receptors control NK cell activation...
NK cell inhibitory receptors prevent tyrosine phosphorylation of the activation receptor 2B4 (CD244)C Watzl
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 165:3545-8. 2000..These results demonstrate that NK inhibitory receptors can interfere with a step as proximal as phosphorylation of an activation receptor...
A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cellsS Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
J Exp Med 189:1093-100. 1999..Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal-fetal interface during pregnancy...
Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244)Philipp Eissmann
Institute for Immunology, University Heidelberg, Germany
Blood 105:4722-9. 2005..We now show that Fyn can also associate with phosphorylated 2B4. Finally, we demonstrate that Fyn and Csk can both phosphorylate 2B4, suggesting a possible mechanism of 2B4 phosphorylation...
Activation, coactivation, and costimulation of resting human natural killer cellsYenan T Bryceson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Immunol Rev 214:73-91. 2006..Conversely, CD16 alone or in synergistic combinations, such as NKG2D and 2B4, signals for phospholipase-C-gamma- and phosphatidylinositol-3-kinase-dependent degranulation...
Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammationHillary H Norris
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA
J Leukoc Biol 82:1531-41. 2007..Expression of gp49B was detected on peripheral eosinophils of control mice and on eosinophils from lungs of mice treated with RW, suggesting a role for gp49B on eosinophils in dampening allergic inflammatory responses...
Line of attack: NK cell specificity and integration of signalsYenan T Bryceson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Curr Opin Immunol 20:344-52. 2008..New insights into the molecular checkpoints for NK cell effector function are highlighted, and underlying reasons for the complexity in NK cell recognition and signaling are proposed...
KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potentialMathias Faure
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 168:6208-14. 2002..Therefore, KIR2DL4 has inhibitory potential in addition to its activating function...
Two modes of lytic granule fusion during degranulation by natural killer cellsDongfang Liu
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Immunol Cell Biol 89:728-38. 2011....
Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cellsS Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 167:1877-81. 2001..These results reveal a functional dichotomy (cytokine production vs cytotoxicity) in the response of resting NK cells, as dictated by the signals of individual receptors...
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodelingSumati Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Proc Natl Acad Sci U S A 109:20596-601. 2012..We propose that a positive function of senescence in healthy tissue is to favor reproduction through the sustained activation of NK cells to remodel maternal vasculature in early pregnancy...
Viral evasion of NK-cell activationSumati Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA
Trends Immunol 26:403-5. 2005..A recent report documents an antagonistic effect of the main HCMV tegument protein, pp65, on NKp30, a natural cytotoxicity-inducing receptor expressed uniquely on NK cells...
Distinct role of rab27a in granule movement at the plasma membrane and in the cytosol of NK cellsDongfang Liu
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA
PLoS ONE 5:e12870. 2010..Therefore, in addition to its documented role in LG delivery to the plasma membrane, Rab27a may restrict LG movement in the cytosol...
A new human gene complex encoding the killer cell inhibitory receptors and related monocyte/macrophage receptorsN Wagtmann
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Curr Biol 7:615-8. 1997
Natural killer cells and mast cells from gp49B null mutant mice are functionalS Rojo
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Mol Cell Biol 20:7178-82. 2000..The healthy status of gp49B(0) mice makes them suitable for testing the role of gp49B in immune responses to infectious agents...
Understanding how combinations of HLA and KIR genes influence diseaseSumati Rajagopalan
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Exp Med 201:1025-9. 2005....
Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cellsDomingo F Barber
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 1727, USA
J Immunol 170:294-9. 2003..Therefore, receptors for LFA-3 and CD48 on resting NK cells strengthen the adhesion mediated by LFA-1...
Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptorD N Burshtyn
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Immunity 4:77-85. 1996..These data imply that the inhibitory function of p58 is dependent on its tyrosine phosphorylation and on recruitment and activation of HCP...
Type I transmembrane receptor with inhibitory function in mouse mast cells and NK cellsS Rojo
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
J Immunol 158:9-12. 1997..These data show that Ig-like receptors with inhibitory properties exist in both species and that mouse mast and NK cells may recognize common inhibitory ligands...
Expression of a killer cell receptor-like gene in plastic regions of the central nervous systemY T Bryceson
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA
J Neuroimmunol 161:177-82. 2005..These results suggest new functions for KIR-like molecules in the CNS...
Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domainsN Wagtmann
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Immunity 2:439-49. 1995..These data revealed a repertoire of NK cells with clonally distributed p58 receptors exhibiting diversity in both extracellular and intracellular domains...
Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patientsYenan T Bryceson
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Blood 110:1906-15. 2007....
Versatile signaling through NKG2DEric O Long
Nat Immunol 3:1119-20. 2002
KIR enrichment at the effector-target cell interface is more sensitive than signaling to the strength of ligand bindingPeter D Borszcz
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada
Eur J Immunol 33:1084-93. 2003..Our findings suggest that the strength of the interaction required to readily detect receptor enrichment exceeds that required for signaling...
A novel phosphotyrosine motif with a critical amino acid at position -2 for the SH2 domain-mediated activation of the tyrosine phosphatase SHP-1D N Burshtyn
Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852, USA
J Biol Chem 272:13066-72. 1997..The contribution of a hydrophobic amino acid two residues upstream of the tyrosine in the SHP-1-binding motif may be an important feature that distinguishes inhibitory receptors from those that provide activation signals...
Zinc bound to the killer cell-inhibitory receptor modulates the negative signal in human NK cellsS Rajagopalan
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 1727, USA
J Immunol 161:1299-305. 1998..The data suggest that complete inhibition of HLA-C-specific NK cells requires a zinc-dependent protein-protein interaction via the amino-terminal end of KIR2D...
Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transferN Wagtmann
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
Immunity 3:801-9. 1995
Essential role of LAT in T cell developmentW Zhang
Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Immunity 10:323-32. 1999..Intrathymic development was blocked within the CD4- CD8- stage. No gross abnormality of NK or platelet function was observed. LAT is thus critical to both T cell activation and development...
Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalizationP A Roche
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
Proc Natl Acad Sci U S A 90:8581-5. 1993..This pathway may represent an important mechanism for loading class II molecules with immunogenic peptides from several endocytic compartments...
