Affinage

CD160

CD160 antigen · UniProt O95971

Length
181 aa
Mass
19.8 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD160 is a GPI-anchored, single Ig-domain receptor on cytotoxic lymphocytes and endothelial cells that delivers context-dependent activating or inhibitory signals through engagement of MHC class I molecules and HVEM. On NK cells and effector CD8+ T cells, CD160 ligation triggers a PI3K→Akt/ERK signaling cascade (with upstream Syk involvement) that drives cytotoxicity and proinflammatory cytokine production (IFN-γ, TNF-α, IL-6, IL-8), and CD160-deficient mice fail to clear mucosal Listeria infection due to impaired CD8+ T cell effector function (PMID:17307798, PMID:23761635, PMID:31022694). Conversely, CD160 engagement via HVEM on chronically stimulated CD8+ T cells delivers a coinhibitory signal that suppresses TCR-driven proliferation independently of PD-1, defining CD160+PD-1+ cells as a deeply exhausted subset (PMID:22916009, PMID:25255144). Structurally, CD160 binds HVEM CRD1 with 1:1 stoichiometry at a site overlapping the BTLA-binding surface but non-overlapping with LIGHT, and HVEM can simultaneously engage LIGHT and CD160 in a ternary complex that partitions distinct immunoregulatory outputs in vivo (PMID:31230945, PMID:34709351).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 Medium

    Establishing that CD160 (BY55) marks a cytotoxic lymphocyte lineage answered the basic question of which cells express this antigen, showing it defines the entire NK compartment in cord blood.

    Evidence Monoclonal antibody staining and functional NK cytotoxicity assays on cord blood and bone marrow lymphocytes

    PMID:8090781

    Open questions at the time
    • No molecular identity or gene structure yet determined
    • Expression on T cell subsets not fully mapped
  2. 1998 High

    Molecular cloning of CD160 established its identity as a GPI-anchored, disulfide-linked multimeric Ig-superfamily receptor preferentially expressed on CD56dim CD16+ NK cells, providing the molecular framework for all subsequent functional studies.

    Evidence cDNA cloning, RNA blot analysis, immunoprecipitation under reducing/non-reducing conditions, flow cytometry

    PMID:9743336

    Open questions at the time
    • Ligand identity unknown
    • Signaling mechanism undefined
    • Function beyond expression pattern not demonstrated
  3. 2002 High

    Two contemporaneous studies revealed CD160's dual functionality: it directly binds HLA-C to trigger NK cytotoxicity and acts as a TCR co-receptor on CD28-negative CD8+ T cells by co-precipitating with p56lck and phospho-ζ chains, establishing CD160 as an activating receptor on both NK cells and T cells.

    Evidence Recombinant soluble protein binding assays, functional cytotoxicity assays, co-immunoprecipitation, T cell proliferation assays

    PMID:11978774 PMID:12486241

    Open questions at the time
    • Signaling intermediates downstream of lck/ζ not mapped
    • p56lck co-IP not validated reciprocally
    • Whether CD160 inhibitory function exists not yet addressed
  4. 2007 High

    Mapping the CD160 signaling cascade in NK cells resolved how a GPI-anchored receptor lacking ITAMs transduces activation signals: PI3K recruitment leads to Akt and ERK phosphorylation with upstream Syk kinase involvement, driving both cytotoxicity and cytokine secretion. Concurrently, CD160 was identified as a co-activator on a novel CD4+ T cell subset in inflammatory skin.

    Evidence Confocal microscopy, pharmacological PI3K/MEK/Syk inhibitors, western blotting, cytotoxicity and cytokine assays; immunohistochemistry of skin biopsies and T cell proliferation assays

    PMID:17218942 PMID:17307798

    Open questions at the time
    • Adaptor protein linking GPI-anchored CD160 to intracellular Syk/PI3K unknown
    • Role of lipid raft partitioning not formally tested
  5. 2009 Medium

    Identification of HVEM as a CD160 ligand and mapping the interaction to HVEM CRD1 reframed CD160 as part of a bidirectional HVEM signaling network, where CRD1 engagement by CD160/BTLA delivers coinhibitory signals while LIGHT engages distinct CRDs for costimulation.

    Evidence Binding assays, HVEM domain deletion/blockade, functional T cell activation assays

    PMID:19426226

    Open questions at the time
    • Review-level summary; primary structural data for the CD160:HVEM interface not yet available
    • Whether CD160 and BTLA compete for HVEM CRD1 or cooperate not resolved
  6. 2010 High

    Demonstration that CD160 signals in CLL B cells to upregulate Bcl-2/Bcl-xL/Mcl-1 via PI3K, promoting survival and cytokine secretion, expanded CD160's role beyond lymphocyte activation to a pro-survival pathway exploited in malignancy.

    Evidence CLL primary cell stimulation, viability and BrdU assays, western blotting for Bcl-2 family, mitochondrial potential assays, PI3K inhibitor pharmacology

    PMID:20164468

    Open questions at the time
    • Whether this represents aberrant expression or a normal B cell function is unclear
    • Ligand triggering CD160 on CLL cells in vivo not identified
  7. 2011 High

    Discovery of CD160 expression on tumor-associated endothelium and demonstration that anti-CD160 antibody CL1-R2 blocks pathological angiogenesis in multiple in vivo models revealed a non-immune function for CD160 in vascular biology.

    Evidence Immunohistochemistry, rabbit cornea neovascularization, mouse oxygen-induced retinopathy, Matrigel plug assay, Doppler ultrasonography

    PMID:21482699

    Open questions at the time
    • Endothelial CD160 signaling pathway not dissected
    • Ligand for CD160 on endothelial cells not identified
    • Whether angiogenic role is HVEM-dependent unknown
  8. 2012 Medium

    Blocking the CD160–HVEM axis on HIV-specific CD8+ T cells restored proliferation and cytokine production, directly demonstrating that CD160-HVEM engagement delivers a coinhibitory signal in chronic infection and that CD160+PD-1+ double-positive cells represent the most exhausted subset with downregulated NF-κB.

    Evidence Anti-HVEM antibody blockade, flow cytometry, microarray transcriptional profiling of HIV-specific CD8+ T cells

    PMID:22916009

    Open questions at the time
    • Blockade targeted HVEM, not CD160 directly, so contributions of BTLA cannot be fully excluded
    • NF-κB downregulation is correlative from transcriptomics
  9. 2013 High

    Selective engagement experiments on human NK cells resolved the paradox of HVEM's dual signaling: HVEM activates CD160 (not BTLA) on CD56dim NK cells to costimulate IFN-γ/TNF-α and hyperphosphorylate ERK1/2 and AKT, while BTLA engagement is inhibitory—demonstrating that the same ligand elicits opposite outcomes through different receptors.

    Evidence Human NK cell stimulation with selective HVEM engagement, phosphoprotein western blotting, cytotoxicity and cytokine ELISA

    PMID:23761635

    Open questions at the time
    • How cell-type context determines whether CD160 or BTLA dominates the response is unknown
  10. 2014 Medium

    Two advances clarified CD160's inhibitory T cell role and isoform biology: CD160 was shown to inhibit TCR signaling independently of PD-1 (blockade of CD160-ligand interaction restored proliferation proportional to CD160+ frequency), and a transmembrane isoform (CD160-TM) was identified that binds HVEM less efficiently than CD160-GPI, with HVEM antibodies paradoxically enhancing CD160-TM binding.

    Evidence CD160 ligand blockade in virus-specific CD8+ T cells; quantitative RT-PCR, time-resolved fluorescence binding, Jurkat activation assays

    PMID:25179432 PMID:25255144

    Open questions at the time
    • CD160-TM signaling pathway not dissected
    • Whether GPI and TM isoforms deliver opposing signals in the same cell unknown
    • Functional significance of antibody-enhanced CD160-TM binding unresolved
  11. 2018 High

    In vivo genetic evidence from CD160-knockout mice demonstrated that CD160 is required for optimal CD8+ T cell effector function during mucosal Listeria infection, with adoptive transfer confirming a cell-intrinsic costimulatory role; separately, TGF-β1 in the HCC tumor microenvironment was shown to suppress IFN-γ production by CD160+ NK cells.

    Evidence CD160−/− mice with oral Listeria infection, adoptive transfer into RAG−/− recipients; flow cytometry and TGF-β1 blockade in HCC patient NK cells with transcriptomic validation

    PMID:30232222 PMID:31022694

    Open questions at the time
    • Whether CD160 costimulation in vivo is HVEM-dependent or MHC-dependent not determined
    • Mechanism by which TGF-β1 suppresses CD160+ NK cell function not elucidated
  12. 2019 High

    Crystal structures of CD160 alone and in complex with HVEM established 1:1 stoichiometry and revealed a unique Ig fold variant, providing the atomic basis for the CD160-HVEM interaction and showing it overlaps the BTLA-binding interface on HVEM.

    Evidence X-ray crystallography, solution biophysics

    PMID:31230945

    Open questions at the time
    • No structure of CD160 bound to MHC class I
    • GPI-anchor and membrane-proximal region not resolved
  13. 2021 High

    The ternary HVEM-LIGHT-CD160 crystal structure demonstrated that HVEM simultaneously engages a TNF ligand and an Ig-domain receptor via non-overlapping surfaces, and genetic knockin mice showed these two binding modes partition distinct immunological functions (bacterial clearance vs. liver inflammation control) in vivo. Separately, IL-16 and CLL-derived extracellular vesicles were shown to upregulate CD160 on T cells, linking the tumor microenvironment to CD160-mediated exhaustion.

    Evidence X-ray crystallography of ternary complex, HVEM mutant knockin mice; CLL plasma cytokine profiling, EV characterization, in vitro IL-16 treatment

    PMID:33931471 PMID:34709351

    Open questions at the time
    • How ternary complex formation affects downstream signaling output quantitatively is unknown
    • Whether EV-transferred CD160 is functional on recipient T cells not formally demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism by which a GPI-anchored receptor (lacking intracellular domains) activates Syk and PI3K remains unresolved—the putative transmembrane adaptor or lipid-raft partner that couples CD160-GPI to intracellular kinases has not been identified.
  • No adaptor protein linking GPI-anchored CD160 to cytoplasmic signaling identified
  • Relative physiological contributions of CD160-GPI vs CD160-TM isoforms undefined
  • Structural basis of CD160 recognition of MHC class I molecules unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 1
Partners
BTLATNFRSF14TNFSF14

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CD160 (BY55) was cloned and identified as a cysteine-rich, glycosylphosphatidylinositol (GPI)-anchored protein of 181 amino acids with a single Ig-like domain weakly homologous to killer inhibitory receptors; it forms tightly disulfide-linked multimers (~80 kDa unreduced, ~27 kDa reduced/carboxyamidomethylated) and is expressed on CD56dim CD16+ NK cells with high cytolytic activity but not on CD56bright CD16- NK cells. cDNA cloning, RNA blot analysis, immunoprecipitation with reduction and carboxyamidomethylation, flow cytometry Journal of immunology High 9743336
2002 CD160 (BY55) acts as a co-receptor in TCR signal transduction: engagement of CD160 on CD28-negative CD8+ effector T cells enhances CD3-induced proliferation, and CD160 co-precipitates with the protein tyrosine kinase p56lck and tyrosine-phosphorylated zeta chains upon TCR-CD3 activation. Anti-CD160 mAb stimulation of primary T cells, proliferation assays, co-immunoprecipitation International immunology Medium 11978774
2002 CD160 expressed on circulating CD56dim NK cells mediates cytotoxic activity against K562 target cells via engagement of HLA-C molecules; direct interaction between recombinant soluble HLA-Cw3 and CD160 proteins was demonstrated, and CD158b inhibitory receptors partially interfered with CD160-mediated cytotoxicity. Functional cytotoxicity assays with anti-CD160 mAb blocking, binding assay with recombinant soluble proteins, flow cytometry Proceedings of the National Academy of Sciences of the United States of America High 12486241
2007 CD160-mediated NK cell effector functions (cytotoxicity and cytokine production including IFN-γ, TNF-α, and IL-6) require phosphatidylinositol 3-kinase (PI3K) recruitment: CD160 engagement induces polarization and co-localization with PI3K, phosphorylation of Akt, activation of the ERK downstream pathway, and involvement of upstream Syk kinase. Confocal microscopy, pharmacological PI3K/MEK/Syk inhibitors, western blotting for phospho-Akt/phospho-ERK/phospho-Syk, cytotoxicity and cytokine release assays International immunology High 17307798
2009 CD160 was identified as a ligand for HVEM (herpesvirus entry mediator) that delivers a coinhibitory signal; the cysteine-rich domain 1 (CRD1) of HVEM is essential for binding of CD160 (and BTLA) but not the costimulatory ligand LIGHT, and deletion or blockade of HVEM CRD1 abolishes CD160/BTLA binding and converts HVEM to a dominant costimulatory molecule. Binding assays, domain deletion/blockade experiments, functional T cell activation assays Immunological reviews Medium 19426226
2010 In CLL B cells (which aberrantly express CD160), CD160 signaling promotes survival by upregulating Bcl-2, Bcl-xL, and Mcl-1, reduces mitochondrial membrane potential collapse and cytochrome c release, induces DNA synthesis and proliferation, stimulates IL-6 and IL-8 secretion, and these effects are dose-dependently suppressed by PI3K inhibitors. CD160 stimulation of primary CLL cells, cell viability assays, western blotting for Bcl-2 family proteins, mitochondrial potential assays, cytochrome c release, BrdU proliferation, ELISA, PI3K inhibitor pharmacology Blood High 20164468
2011 CD160 is expressed on endothelial cells of newly formed blood vessels in human colon carcinoma and mouse melanoma but not in healthy tissue vessels; a monoclonal antibody (CL1-R2) targeting CD160 exerted antiangiogenic effects in multiple animal models (rabbit cornea FGF2-induced neovascularization, mouse oxygen-induced retinopathy, mouse Matrigel plug), and combined with chemotherapy caused regression and normalization of tumor vasculature. Immunohistochemistry, rabbit cornea assay, mouse oxygen-induced retinopathy, Matrigel plug assay, Doppler ultrasonography, intravital microscopy, histology The Journal of experimental medicine High 21482699
2011 CD160 is a unique GPI-anchored activating NK receptor that signals through PI3K recruitment and lacks intrinsic ITAMs; it recognizes both MHC class Ia and Ib molecules and triggers cytotoxicity and proinflammatory cytokine production (IFN-γ, TNF-α, IL-6, IL-8, MIP1-β) at levels exceeding those induced by CD16 engagement. Functional NK cytotoxicity and cytokine release assays, specific antibody engagement, comparison with CD16-mediated responses Immunology letters Medium 21324341
2012 Blocking the CD160–HVEM interaction with anti-HVEM antibody increased HIV-specific CD8 T cell proliferation and cytokine production, demonstrating that CD160 signals through HVEM to suppress T cell function; co-expression of CD160 and PD-1 on CD8 T cells defines a highly exhausted subset with downregulated NFκB signaling and upregulated inhibitors of T cell survival. HVEM blockade functional assay, flow cytometry, transcriptional profiling (microarray) PLoS pathogens Medium 22916009
2013 HVEM specifically activates CD160 on human CD56dim NK cells: HVEM engagement costimulated NK cells via CD160 (not BTLA), enhanced IFN-γ and TNF-α secretion induced by type I IFN and IL-2, and caused rapid hyperphosphorylation of ERK1/2 and AKT and enhanced cytolysis of target cells. In contrast, HVEM activation of BTLA reduced cytolysis. Human NK cell stimulation assays, selective receptor engagement with HVEM ligand, phosphoprotein western blotting (ERK1/2, AKT), cytotoxicity assays, cytokine ELISA Journal of immunology High 23761635
2014 CD160 negatively regulates TCR-mediated signaling independently of PD-1: CD160+ CD8 T cells have reduced proliferation and perforin expression, and blockade of the CD160/CD160-ligand interaction restores proliferation in proportion to the ex vivo frequency of CD160+ cells. CD160 expression was not induced by T cell activation unlike PD-1. CD160 ligand blockade functional assay, flow cytometry, proliferation assays with virus-specific CD8 T cells (influenza, EBV, CMV antigens) PLoS pathogens Medium 25255144
2014 CD160 exists in two isoforms (CD160-GPI and CD160-TM) both expressed in human primary CD4+ and CD8+ T cells; both isoforms bind HVEM, though CD160-TM binds less efficiently. HVEM antibodies blocked binding to CD160-GPI but paradoxically enhanced binding to CD160-TM, suggesting antibody-induced HVEM multimerization or conformational change. CD160-GPI triggering (via bead-bound HVEM-Fc or anti-CD160 mAb) enhanced Jurkat cell activation, consistent with a costimulatory role. Quantitative RT-PCR, flow cytometry, Time-Resolved Fluorescence binding assay, Jurkat cell activation assay Journal of translational medicine Medium 25179432
2007 A novel CD160+CD4+ T cell subset was identified in inflammatory skin lesions (atopic dermatitis, contact dermatitis, psoriasis); CD160 engagement acted as a co-activator receptor for CD3-induced proliferation in this subset. CD160 transcripts could be induced in IL-2 or IL-15-activated CD4+ peripheral blood lymphocytes. Immunohistochemistry of skin biopsies, RT-PCR, T cell proliferation assay with anti-CD160 co-stimulation The Journal of investigative dermatology Medium 17218942
2019 Crystal structures of the human CD160 extracellular domain alone and in complex with HVEM were solved; CD160 adopts a unique variation of the immunoglobulin fold, exists as a monomer in solution, and the CD160:HVEM assembly exhibits 1:1 stoichiometry with a binding interface similar to that of the BTLA:HVEM complex. X-ray crystallography, solution biophysics Structure High 31230945
2021 Crystal structures of HVEM-LIGHT-CD160 ternary complex demonstrated that HVEM can interact simultaneously with LIGHT (TNF ligand) and CD160 (Ig superfamily member) via distinct non-overlapping surfaces; HVEM mutants selectively recognizing either TNF or Ig ligands showed that LIGHT mediates bacterial clearance in the intestine while Ig ligands (including CD160) ameliorate liver inflammation in vivo. X-ray crystallography (ternary complex), site-directed mutagenesis, knockin mouse models with selective HVEM mutants The Journal of experimental medicine High 34709351
2018 CD160 provides costimulatory signals to CD8+ T cells required for optimal clearance of oral Listeria monocytogenes infection: CD160-/- mice failed to clear infection efficiently, with reduced frequencies of granzyme B+ intraepithelial lymphocytes and granzyme B+, IFN-γ+TNF-α+ splenic CD8+ T cells. Adoptive transfer of CD160-/- CD8+ T cells into RAG-/- recipients caused higher mortality and bacterial burden than WT CD8+ T cells. NK cells did not contribute to impaired clearance. CD160 knockout mice, oral infection model, flow cytometry, adoptive transfer experiments, RAG-/- recipients ImmunoHorizons High 31022694
2018 Reduced CD160 expression on intratumoral NK cells in HCC impairs IFN-γ production; TGFβ1 in the tumor microenvironment interferes with IFN-γ production by CD160+ NK cells, and TGFβ1 blockade specifically restores IFN-γ production by CD160+ NK cells. Transcriptomic analysis of sorted CD160+ vs CD160- NK cells confirmed functional activation signatures in CD160+ cells. Flow cytometry, transcriptomic microarray/gene set enrichment analysis of sorted NK cell subsets, TGFβ1 blockade functional assay, histology of patient tumors Cancer research Medium 30232222
2021 In patients with CLL, IL-16 in the plasma (highly elevated) directly upregulates CD160 expression on T cells, and extracellular vesicles (EVs) from CLL plasma serve as an additional source of CD160 that can be taken up by T cells, contributing to CD160-associated T cell exhaustion. Plasma cytokine profiling, EV characterization, in vitro IL-16 treatment of T cells, flow cytometry Journal for immunotherapy of cancer Medium 33931471
1994 The BY55 (CD160) antigen (~80 kDa on the cell surface) marks cytotoxic lymphocytes; within cord blood, BY55+ cells correspond exclusively to a CD3- subset that contains the entire natural killer activity, demonstrating that CD160 expression is restricted to cytotoxic NK and T cell lineages. BY55 monoclonal antibody staining, flow cytometry, functional NK cytotoxicity assays on cord blood and bone marrow lymphocytes Proceedings of the National Academy of Sciences of the United States of America Medium 8090781
2006 Murine CD160 is expressed predominantly on CD44high CD8+ memory T cells (both effector memory and central memory) and recently activated CD8+ T cells; CD160+ CD8+ T cells from OT-1 transgenic mice produce IFN-γ more rapidly than CD160- CD8+ T cells upon antigen stimulation, and soluble CD160 is released after in vitro CD3-mediated stimulation. Anti-murine CD160 mAb generation, flow cytometry, in vitro stimulation assays, intracellular IFN-γ staining Immunology letters Medium 16764942

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Mouse CD1-specific NK1 T cells: development, specificity, and function. Annual review of immunology 986 9143699
2002 A natural killer T (NKT) cell developmental pathway iInvolving a thymus-dependent NK1.1(-)CD4(+) CD1d-dependent precursor stage. The Journal of experimental medicine 282 11927628
1998 The tachykinin NK1 receptor. Part II: Distribution and pathophysiological roles. Neuropeptides 248 9571643
2009 The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Immunological reviews 247 19426226
2009 CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells. European journal of immunology 232 19830744
1999 Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. The Journal of experimental medicine 232 10190898
1999 Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists. Trends in pharmacological sciences 222 10671176
1998 Differentiation of human NK cells into NK1 and NK2 subsets. Journal of immunology (Baltimore, Md. : 1950) 222 9834059
2002 Neurobiology of substance P and the NK1 receptor. The Journal of clinical psychiatry 219 12562137
2004 Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 216 14666114
1999 The tachykinin NK1 receptor in the brain: pharmacology and putative functions. European journal of pharmacology 176 10443564
1997 The tachykinin NK1 receptor. Part I: ligands and mechanisms of cellular activation. Neuropeptides 173 9574822
2015 Biological and Pharmacological Aspects of the NK1-Receptor. BioMed research international 161 26421291
2014 Involvement of substance P and the NK-1 receptor in human pathology. Amino acids 157 24705689
2009 HVEM/LIGHT/BTLA/CD160 cosignaling pathways as targets for immune regulation. Journal of leukocyte biology 133 20007250
2007 Development and function of murine B220+CD11c+NK1.1+ cells identify them as a subset of NK cells. The Journal of experimental medicine 130 17923504
2012 CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. PLoS pathogens 123 22916009
1996 Heparin induces dimerization and confers proliferative activity onto the hepatocyte growth factor antagonists NK1 and NK2. The Journal of cell biology 123 8636243
2013 Involvement of substance P and the NK-1 receptor in cancer progression. Peptides 118 23933301
1998 Cloning of BY55, a novel Ig superfamily member expressed on NK cells, CTL, and intestinal intraepithelial lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 114 9743336
2002 Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. The Journal of clinical psychiatry 113 12562139
2006 Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells. Journal of immunology (Baltimore, Md. : 1950) 110 16751398
2002 Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America 108 12486241
2003 Substance P via NK1 receptor facilitates hyperactive bladder afferent signaling via action of ROS. American journal of physiology. Renal physiology 87 12620925
2006 Long-term retention of mature NK1.1+ NKT cells in the thymus. Journal of immunology (Baltimore, Md. : 1950) 86 16547241
1997 NK1.1+ CD4+ T cells lose NK1.1 expression upon in vitro activation. Journal of immunology (Baltimore, Md. : 1950) 77 9164926
2013 CD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cytolytic function by NK cells. Journal of immunology (Baltimore, Md. : 1950) 74 23761635
2011 The NK-1 receptor: a new target in cancer therapy. Current drug targets 73 21226668
2002 The NK1 receptor mediates both the hyperalgesia and the resistance to morphine in mice lacking noradrenaline. Proceedings of the National Academy of Sciences of the United States of America 71 11805341
2005 Species differences in tachykinin receptor distribution: further evidence that the substance P (NK1) receptor predominates in human brain. The Journal of comparative neurology 67 16127708
2014 CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. PLoS pathogens 66 25255144
2011 CD160: a unique activating NK cell receptor. Immunology letters 66 21324341
2000 CD1d-specific NK1.1+ T cells with a transgenic variant TCR. Journal of immunology (Baltimore, Md. : 1950) 65 10861049
2001 Localization of NK1 and NK3 receptors in guinea-pig brain. Regulatory peptides 60 11179779
2003 Aprepitant--a novel NK1-receptor antagonist. Expert opinion on pharmacotherapy 56 14640927
2002 BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression. International immunology 55 11978774
2001 The NK1 receptor is essential for the full expression of noxious inhibitory controls in the mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 11157089
2000 The role of tachykinins via NK1 receptors in progression of human gliomas. Life sciences 51 10954033
2002 Clinical experience with substance P receptor (NK1) antagonists in depression. The Journal of clinical psychiatry 50 12562140
2005 Visualization and quantification of neurokinin-1 (NK1) receptors in the human brain. Molecular imaging and biology 48 16155744
2002 Behavioral and physiologic effects of genetic or pharmacologic inactivation of the substance P receptor (NK1). The Journal of clinical psychiatry 48 12562138
1994 BY55 monoclonal antibody delineates within human cord blood and bone marrow lymphocytes distinct cell subsets mediating cytotoxic activity. Proceedings of the National Academy of Sciences of the United States of America 48 8090781
1990 In vitro and in vivo analysis of bone marrow-derived CD3+, CD4-, CD8-, NK1.1+ cell lines. Cellular immunology 48 2143439
2018 Reduced CD160 Expression Contributes to Impaired NK-cell Function and Poor Clinical Outcomes in Patients with HCC. Cancer research 47 30232222
2000 Substance P (NK1) receptors in the cingulate cortex in unipolar and bipolar mood disorder and schizophrenia. Biological psychiatry 47 10650452
1996 Expression of tachykinin NK1 receptor mRNA in dorsal root ganglia of the mouse. Brain research. Molecular brain research 47 8717372
2002 The murine neurokinin NK1 receptor gene contributes to the adult hypoxic facilitation of ventilation. The European journal of neuroscience 46 12492418
2002 New insights into the antidepressant actions of substance P (NK1 receptor) antagonists. Canadian journal of physiology and pharmacology 44 12056558
2010 CD160 signaling mediates PI3K-dependent survival and growth signals in chronic lymphocytic leukemia. Blood 42 20164468
2009 Behavioural and neurochemical abnormalities in mice lacking functional tachykinin-1 (NK1) receptors: a model of attention deficit hyperactivity disorder. Neuropharmacology 42 19748515
2002 Elucidating the antidepressant actions of substance P (NK1 receptor) antagonists. Current opinion in investigational drugs (London, England : 2000) 42 12020057
2015 NK-1 Antagonists and Itch. Handbook of experimental pharmacology 41 25861784
2021 Expanded antigen-experienced CD160+CD8+effector T cells exhibit impaired effector functions in chronic lymphocytic leukemia. Journal for immunotherapy of cancer 40 33931471
2014 Involvement of substance P and the NK-1 receptor in pancreatic cancer. World journal of gastroenterology 40 24605029
2006 Characterization of murine CD160+ CD8+ T lymphocytes. Immunology letters 40 16764942
2014 NK1.1+ CD8+ T cells escape TGF-β control and contribute to early microbial pathogen response. Nature communications 39 25284210
2012 The NK1 receptor antagonist L822429 reduces heroin reinforcement. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39 23303056
2002 Stereospecific blockade of marble-burying behaviour in mice by selective, non-peptidergic neurokinin1 (NK1) receptor antagonists. Neuropharmacology 38 11985826
2007 Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation. Blood 37 17895403
2014 Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Experimental brain research 36 24969614
2011 A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor. The Journal of experimental medicine 36 21482699
2019 Structural Basis of CD160:HVEM Recognition. Structure (London, England : 1993) 35 31230945
2000 Localisation of tachykinin NK1 and NK3 receptors in the human prefrontal and visual cortex. Neuroscience letters 35 10754218
1995 Striatal neurones displaying substance P (NK1) receptor immunoreactivity in human and non-human primates. Neuroreport 35 7605934
2021 Granzyme A and CD160 expression delineates ILC1 with graded functions in the mouse liver. European journal of immunology 34 34347289
2008 17beta-estradiol suppresses cytotoxicity and proliferative capacity of murine splenic NK1.1+ cells. Cellular & molecular immunology 34 18954559
1990 The rabbit jugular vein is a contractile NK-1 receptor system. European journal of pharmacology 34 2163859
2019 NK-1 Receptor Antagonists and Pruritus: Review of Current Literature. Dermatology and therapy 33 31190215
2018 Crystal structure of the human NK1 tachykinin receptor. Proceedings of the National Academy of Sciences of the United States of America 32 30538204
2019 The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy. Pharmaceutics 31 31480582
2009 Murine endometrial and decidual NK1.1+ natural killer cells display a B220+CD11c+ cell surface phenotype. Biology of reproduction 31 19369645
2007 CD160-activating NK cell effector functions depend on the phosphatidylinositol 3-kinase recruitment. International immunology 30 17307798
2004 Substance P (NK1) and somatostatin (sst2A) receptor immunoreactivity in NTS-projecting rat dorsal horn neurones activated by nociceptive afferent input. Journal of chemical neuroanatomy 30 15261332
2000 Differential regulation of Ly49 expression on CD4+ and CD4-CD8- (double negative) NK1.1+ T cells. European journal of immunology 30 11009081
2018 CD160 Stimulates CD8+ T Cell Responses and Is Required for Optimal Protective Immunity to Listeria monocytogenes. ImmunoHorizons 29 31022694
2000 Tachykinin NK1 and NK3 receptors in the prefrontal cortex of the human brain. Clinical and experimental pharmacology & physiology 29 11071316
2007 Identification of a novel CD160+ CD4+ T-lymphocyte subset in the skin: a possible role for CD160 in skin inflammation. The Journal of investigative dermatology 28 17218942
2006 [3H]GR205171 displays similar NK1 receptor binding profile in gerbil and human brain. British journal of pharmacology 28 16501582
2003 VR1-positive primary afferents contact NK1-positive spinoparabrachial neurons. The Journal of comparative neurology 28 12687689
2002 The human tachykinin NK1 (short form) and tachykinin NK4 receptor: a reappraisal. European journal of pharmacology 28 11864635
2002 Neurokinin NK1- and NK3-immunoreactive neurons in serotonergic cell groups in the rat brain. Neuroscience letters 28 11950514
2002 [Why are substance P(NK1)-receptor antagonists ineffective in pain treatment?]. Der Anaesthesist 28 12063723
2000 Disulfide bridge engineering in the tachykinin NK1 receptor. Biochemistry 28 10651631
1997 Generation of NK1.1+ T cell antigen receptor alpha/beta+ thymocytes associated with intact thymic structure. Proceedings of the National Academy of Sciences of the United States of America 27 9122219
2019 Carboplatin chemoresistance is associated with CD11b+/Ly6C+ myeloid release and upregulation of TIGIT and LAG3/CD160 exhausted T cells. Molecular immunology 26 31862674
2007 Sensitivity of NK1.1-negative NKT cells to transgenic BATF defines a role for activator protein-1 in the expansion and maturation of immature NKT cells in the thymus. Journal of immunology (Baltimore, Md. : 1950) 26 17182540
1993 NK1 and NK2 receptors mediate tachykinin and resiniferatoxin-induced bronchospasm in guinea pigs. The American review of respiratory disease 26 7692776
2023 TCRαβ+NK1.1-CD4-CD8- double-negative T cells inhibit central and peripheral inflammation and ameliorate ischemic stroke in mice. Theranostics 25 36793857
2009 NK1 receptor antagonism and emotional processing in healthy volunteers. Journal of psychopharmacology (Oxford, England) 25 19351798
2021 HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160. The Journal of experimental medicine 24 34709351
2014 CD160 isoforms and regulation of CD4 and CD8 T-cell responses. Journal of translational medicine 24 25179432
2011 A pharmacokinetic PET study of NK₁ receptor occupancy. European journal of nuclear medicine and molecular imaging 24 21993526
2004 The role of intrahepatic CD8+ T cell trapping and NK1.1+ cells in liver-mediated immune regulation. Clinical immunology (Orlando, Fla.) 24 15093555
2001 Differential expression of functionally identified and immunohistochemically identified NK(1) receptors on sympathetic neurons. Journal of neurophysiology 24 11353005
1993 Identification of both NK1 and NK2 receptors in guinea-pig airways. British journal of pharmacology 24 7694756
2016 α-Galactosylceramide-activated murine NK1.1(+) invariant-NKT cells in the myometrium induce miscarriages in mice. European journal of immunology 23 27198610
2010 Immunolocalization of NK-1 receptor and Substance P in human normal placenta. Placenta 23 20430440
1998 Natural killer cell proliferation induced by anti-NK1.1 and IL-2. Immunology and cell biology 23 9619484
1996 Functional characterization of NK1.1 + Ly-6C+ cells. Immunology letters 23 9030975
2005 Differentiation of NK1 and NK2 cells. Critical reviews in immunology 22 16167886